Misplaced Pages

#62937

85-596: 1OGS , 1Y7V , 2F61 , 2J25 , 2NSX , 2NT0 , 2NT1 , 2V3D , 2V3E , 2V3F , 2VT0 , 2WCG , 2WKL , 2XWD , 2XWE , 3GXD , 3GXF , 3GXI , 3GXM , 3KE0 , 3KEH , 3RIK , 3RIL 2629 14466 ENSG00000262446 ENSG00000177628 ENSMUSG00000028048 P04062 P17439 NM_001171811 NM_001171812 NM_001077411 NM_008094 NP_000148 NP_001005741 NP_001005742 NP_001165282 NP_001165283 NP_001070879 NP_032120 β-Glucocerebrosidase (also called acid β-glucosidase , D -glucosyl-N-acylsphingosine glucohydrolase , or GCase )

170-487: A catalytic triad , stabilize charge build-up on the transition states using an oxyanion hole , complete hydrolysis using an oriented water substrate. Enzymes are not rigid, static structures; instead they have complex internal dynamic motions – that is, movements of parts of the enzyme's structure such as individual amino acid residues, groups of residues forming a protein loop or unit of secondary structure , or even an entire protein domain . These motions give rise to

255-489: A conformational ensemble of slightly different structures that interconvert with one another at equilibrium . Different states within this ensemble may be associated with different aspects of an enzyme's function. For example, different conformations of the enzyme dihydrofolate reductase are associated with the substrate binding, catalysis, cofactor release, and product release steps of the catalytic cycle, consistent with catalytic resonance theory . Substrate presentation

340-434: A lysosomal storage disease characterized by an accumulation of glucocerebrosides in macrophages that infiltrate many vital organs. Mutations in the glucocerebrosidase gene are also associated with Parkinson's disease . A related pseudogene is approximately 12 kb downstream of this gene on chromosome 1 . Alternative splicing results in multiple transcript variants encoding the same protein. Alglucerase (Ceredase)

425-615: A ); similarly for the reciprocal lattice. So, in this common case, the Miller indices ( ℓmn ) and [ ℓmn ] both simply denote normals/directions in Cartesian coordinates . For cubic crystals with lattice constant a , the spacing d between adjacent (ℓmn) lattice planes is (from above): Because of the symmetry of cubic crystals, it is possible to change the place and sign of the integers and have equivalent directions and planes: For face-centered cubic (fcc) and body-centered cubic (bcc) lattices,

510-424: A ccp arrangement of atoms is the face-centered cubic (fcc) unit cell. This is not immediately obvious as the closely packed layers are parallel to the {111} planes of the fcc unit cell. There are four different orientations of the close-packed layers. One important characteristic of a crystalline structure is its atomic packing factor (APF). This is calculated by assuming that all the atoms are identical spheres, with

595-452: A critical role in determining many physical properties, such as cleavage , electronic band structure , and optical transparency . Crystal structure is described in terms of the geometry of arrangement of particles in the unit cells. The unit cell is defined as the smallest repeating unit having the full symmetry of the crystal structure. The geometry of the unit cell is defined as a parallelepiped , providing six lattice parameters taken as

680-404: A crystal lattice are described by the three-value Miller index notation. This syntax uses the indices h , k , and ℓ as directional parameters. By definition, the syntax ( hkℓ ) denotes a plane that intercepts the three points a 1 / h , a 2 / k , and a 3 / ℓ , or some multiple thereof. That is, the Miller indices are proportional to the inverses of the intercepts of the plane with

765-413: A crystal. Likewise, the crystallographic planes are geometric planes linking nodes. Some directions and planes have a higher density of nodes. These high density planes have an influence on the behavior of the crystal as follows: Some directions and planes are defined by symmetry of the crystal system. In monoclinic, trigonal, tetragonal, and hexagonal systems there is one unique axis (sometimes called

850-507: A cubic cell, the Miller indices of a plane are the Cartesian components of a vector normal to the plane. Considering only ( hkℓ ) planes intersecting one or more lattice points (the lattice planes ), the distance d between adjacent lattice planes is related to the (shortest) reciprocal lattice vector orthogonal to the planes by the formula The crystallographic directions are geometric lines linking nodes ( atoms , ions or molecules ) of

935-474: A first step and then checks that the product is correct in a second step. This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity mammalian polymerases. Similar proofreading mechanisms are also found in RNA polymerase , aminoacyl tRNA synthetases and ribosomes . Conversely, some enzymes display enzyme promiscuity , having broad specificity and acting on

SECTION 10

#1732852696063

1020-599: A lattice system. Of the 32 point groups that exist in three dimensions, most are assigned to only one lattice system, in which case the crystal system and lattice system both have the same name. However, five point groups are assigned to two lattice systems, rhombohedral and hexagonal, because both lattice systems exhibit threefold rotational symmetry. These point groups are assigned to the trigonal crystal system. In total there are seven crystal systems: triclinic, monoclinic, orthorhombic, tetragonal, trigonal, hexagonal, and cubic. The crystallographic point group or crystal class

1105-653: A molecular mass of 59,700 Da . β-Glucocerebrosidase is a member of the glycoside hydrolase family 30 and consists of three distinct domains (I-III). Domain I (residues 1–27 and 383–414) forms a three-stranded anti-parallel β-sheet. This domain contains two disulfide bridges that are necessary for correct folding, as well as a glycosylated residue (Asn19) that is required for catalytic activity in vivo. Domain II (residues 30–75 and 431–497) consists of two β-sheets that resemble an immunoglobulin fold . Domain III (residues 76–381 and 416–430)

1190-464: A quantitative theory of enzyme kinetics, which is referred to as Michaelis–Menten kinetics . The major contribution of Michaelis and Menten was to think of enzyme reactions in two stages. In the first, the substrate binds reversibly to the enzyme, forming the enzyme-substrate complex. This is sometimes called the Michaelis–Menten complex in their honor. The enzyme then catalyzes the chemical step in

1275-413: A radius large enough that each sphere abuts on the next. The atomic packing factor is the proportion of space filled by these spheres which can be worked out by calculating the total volume of the spheres and dividing by the volume of the cell as follows: Another important characteristic of a crystalline structure is its coordination number (CN). This is the number of nearest neighbours of a central atom in

1360-439: A range of different physiologically relevant substrates. Many enzymes possess small side activities which arose fortuitously (i.e. neutrally ), which may be the starting point for the evolutionary selection of a new function. To explain the observed specificity of enzymes, in 1894 Emil Fischer proposed that both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another. This

1445-451: A species' normal level; as a result, enzymes from bacteria living in volcanic environments such as hot springs are prized by industrial users for their ability to function at high temperatures, allowing enzyme-catalysed reactions to be operated at a very high rate. Enzymes are usually much larger than their substrates. Sizes range from just 62 amino acid residues, for the monomer of 4-oxalocrotonate tautomerase , to over 2,500 residues in

1530-446: A steady level inside the cell. For example, NADPH is regenerated through the pentose phosphate pathway and S -adenosylmethionine by methionine adenosyltransferase . This continuous regeneration means that small amounts of coenzymes can be used very intensively. For example, the human body turns over its own weight in ATP each day. As with all catalysts, enzymes do not alter the position of

1615-442: A thermodynamically unfavourable one so that the combined energy of the products is lower than the substrates. For example, the hydrolysis of ATP is often used to drive other chemical reactions. Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products. The rate data used in kinetic analyses are commonly obtained from enzyme assays . In 1913 Leonor Michaelis and Maud Leonora Menten proposed

1700-505: A two-step mechanism. In the first step, E340 performs a nucleophilic attack at the carbon of the O-glycosidic linkage to displace the sphingosine moiety, which is simultaneously protonated by E235 as it is released from the active site. In the second step, glucose is hydrolyzed from the E340 residue to regenerate the active enzyme. β-Glucocerebrosidase is maximally active at pH 5.5, the pH of

1785-457: Is k cat , also called the turnover number , which is the number of substrate molecules handled by one active site per second. The efficiency of an enzyme can be expressed in terms of k cat / K m . This is also called the specificity constant and incorporates the rate constants for all steps in the reaction up to and including the first irreversible step. Because the specificity constant reflects both affinity and catalytic ability, it

SECTION 20

#1732852696063

1870-838: Is orotidine 5'-phosphate decarboxylase , which allows a reaction that would otherwise take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, nor do they alter the equilibrium of a reaction. Enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules: inhibitors are molecules that decrease enzyme activity, and activators are molecules that increase activity. Many therapeutic drugs and poisons are enzyme inhibitors. An enzyme's activity decreases markedly outside its optimal temperature and pH , and many enzymes are (permanently) denatured when exposed to excessive heat, losing their structure and catalytic properties. Some enzymes are used commercially, for example, in

1955-421: Is a process where the enzyme is sequestered away from its substrate. Enzymes can be sequestered to the plasma membrane away from a substrate in the nucleus or cytosol. Or within the membrane, an enzyme can be sequestered into lipid rafts away from its substrate in the disordered region. When the enzyme is released it mixes with its substrate. Alternatively, the enzyme can be sequestered near its substrate to activate

2040-414: Is an enzyme with glucosylceramidase activity ( EC 3.2.1.45 ) that cleaves by hydrolysis the β-glycosidic linkage of the chemical glucocerebroside , an intermediate in glycolipid metabolism that is abundant in cell membranes (particularly skin cells). It is localized in the lysosome , where it remains associated with the lysosomal membrane. β-Glucocerebrosidase is 497 amino acids in length and has

2125-437: Is described by "EC" followed by a sequence of four numbers which represent the hierarchy of enzymatic activity (from very general to very specific). That is, the first number broadly classifies the enzyme based on its mechanism while the other digits add more and more specificity. The top-level classification is: These sections are subdivided by other features such as the substrate, products, and chemical mechanism . An enzyme

2210-749: Is fully specified by four numerical designations. For example, hexokinase (EC 2.7.1.1) is a transferase (EC 2) that adds a phosphate group (EC 2.7) to a hexose sugar, a molecule containing an alcohol group (EC 2.7.1). Sequence similarity . EC categories do not reflect sequence similarity. For instance, two ligases of the same EC number that catalyze exactly the same reaction can have completely different sequences. Independent of their function, enzymes, like any other proteins, have been classified by their sequence similarity into numerous families. These families have been documented in dozens of different protein and protein family databases such as Pfam . Non-homologous isofunctional enzymes . Unrelated enzymes that have

2295-401: Is homologous to a TIM barrel and is a highly conserved domain among glycoside hydrolases . Domain III harbors the active site, which binds the substrate glucocerebroside in close proximity to the catalytic residues E340 and E235. Domains I and III are tightly associated, while domains II and III are joined by a disordered linker. Crystal structures indicate that β-glucocerebrosidase binds

2380-473: Is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase . Examples are lactase , alcohol dehydrogenase and DNA polymerase . Different enzymes that catalyze the same chemical reaction are called isozymes . The International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the EC numbers (for "Enzyme Commission") . Each enzyme

2465-418: Is often referred to as "the lock and key" model. This early model explains enzyme specificity, but fails to explain the stabilization of the transition state that enzymes achieve. In 1958, Daniel Koshland suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continuously reshaped by interactions with the substrate as the substrate interacts with

2550-462: Is only one of several important kinetic parameters. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the Michaelis–Menten constant ( K m ), which is the substrate concentration required for an enzyme to reach one-half its maximum reaction rate; generally, each enzyme has a characteristic K M for a given substrate. Another useful constant

2635-404: Is seen. This is shown in the saturation curve on the right. Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES complex. At the maximum reaction rate ( V max ) of the enzyme, all the enzyme active sites are bound to substrate, and the amount of ES complex is the same as the total amount of enzyme. V max

Glucocerebrosidase - Misplaced Pages Continue

2720-403: Is the ribosome which is a complex of protein and catalytic RNA components. Enzymes must bind their substrates before they can catalyse any chemical reaction. Enzymes are usually very specific as to what substrates they bind and then the chemical reaction catalysed. Specificity is achieved by binding pockets with complementary shape, charge and hydrophilic / hydrophobic characteristics to

2805-403: Is the mathematical group comprising the symmetry operations that leave at least one point unmoved and that leave the appearance of the crystal structure unchanged. These symmetry operations include Rotation axes (proper and improper), reflection planes, and centers of symmetry are collectively called symmetry elements . There are 32 possible crystal classes. Each one can be classified into one of

2890-790: Is useful for comparing different enzymes against each other, or the same enzyme with different substrates. The theoretical maximum for the specificity constant is called the diffusion limit and is about 10 to 10 (M s ). At this point every collision of the enzyme with its substrate will result in catalysis, and the rate of product formation is not limited by the reaction rate but by the diffusion rate. Enzymes with this property are called catalytically perfect or kinetically perfect . Example of such enzymes are triose-phosphate isomerase , carbonic anhydrase , acetylcholinesterase , catalase , fumarase , β-lactamase , and superoxide dismutase . The turnover of such enzymes can reach several million reactions per second. But most enzymes are far from perfect:

2975-611: The DNA polymerases ; here the holoenzyme is the complete complex containing all the subunits needed for activity. Coenzymes are small organic molecules that can be loosely or tightly bound to an enzyme. Coenzymes transport chemical groups from one enzyme to another. Examples include NADH , NADPH and adenosine triphosphate (ATP). Some coenzymes, such as flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), thiamine pyrophosphate (TPP), and tetrahydrofolate (THF), are derived from vitamins . These coenzymes cannot be synthesized by

3060-489: The glucose moiety and adjacent O-glycosydic bond of glucocerebroside . The two aliphatic chains of glucocerebroside may remain associated with the lysosomal bilayer or interact with the activating protein Saposin C. Consistent with other glycoside hydrolases, the mechanism of glucocerebroside hydrolysis by β-glucocerebrosidase involves acid/base catalysis by two glutamic acid residues (E340 and E235) and precedes through

3145-511: The law of mass action , which is derived from the assumptions of free diffusion and thermodynamically driven random collision. Many biochemical or cellular processes deviate significantly from these conditions, because of macromolecular crowding and constrained molecular movement. More recent, complex extensions of the model attempt to correct for these effects. Enzyme reaction rates can be decreased by various types of enzyme inhibitors. A competitive inhibitor and substrate cannot bind to

3230-556: The mannose-6-phosphate pathway for trafficking to the lysosome . A study in I-cell disease fibroblasts (in which the phosphotransferase that puts Mannose 6-phosphate on proteins to target them to the lysosome is defective) showed targeting of GCase to the lysosome independent of the M6P pathway. The lysosomal transporter and integral membrane protein LIMP-2 (Lysosomal Integral Membrane Protein 2)

3315-420: The principal axis ) which has higher rotational symmetry than the other two axes. The basal plane is the plane perpendicular to the principal axis in these crystal systems. For triclinic, orthorhombic, and cubic crystal systems the axis designation is arbitrary and there is no principal axis. For the special case of simple cubic crystals, the lattice vectors are orthogonal and of equal length (usually denoted

3400-591: The trigonal crystal system ), orthorhombic , monoclinic and triclinic . Bravais lattices , also referred to as space lattices , describe the geometric arrangement of the lattice points, and therefore the translational symmetry of the crystal. The three dimensions of space afford 14 distinct Bravais lattices describing the translational symmetry. All crystalline materials recognized today, not including quasicrystals , fit in one of these arrangements. The fourteen three-dimensional lattices, classified by lattice system, are shown above. The crystal structure consists of

3485-400: The ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules , also called ribozymes . They are sometimes described as a type of enzyme rather than being like an enzyme, but even in

Glucocerebrosidase - Misplaced Pages Continue

3570-437: The active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in redox reactions. Enzymes that require a cofactor but do not have one bound are called apoenzymes or apoproteins . An enzyme together with the cofactor(s) required for activity is called a holoenzyme (or haloenzyme). The term holoenzyme can also be applied to enzymes that contain multiple protein subunits, such as

3655-456: The active site of the enzyme. β-Glucocerebrosidase is specifically and irreversibly inhibited by the glucose analog Conduritol B epoxide. Conduritol B epoxide binds to the GCase active site, where the enzyme cleaves its epoxide ring, forming a permanent covalent bond between the enzyme and the inhibitor. Initially, GCase was thought to be one of the few lysosomal enzymes that does not follow

3740-502: The active site. Organic cofactors can be either coenzymes , which are released from the enzyme's active site during the reaction, or prosthetic groups , which are tightly bound to an enzyme. Organic prosthetic groups can be covalently bound (e.g., biotin in enzymes such as pyruvate carboxylase ). An example of an enzyme that contains a cofactor is carbonic anhydrase , which uses a zinc cofactor bound as part of its active site. These tightly bound ions or molecules are usually found in

3825-407: The animal fatty acid synthase . Only a small portion of their structure (around 2–4 amino acids) is directly involved in catalysis: the catalytic site. This catalytic site is located next to one or more binding sites where residues orient the substrates. The catalytic site and binding site together compose the enzyme's active site . The remaining majority of the enzyme structure serves to maintain

3910-578: The average values of k c a t / K m {\displaystyle k_{\rm {cat}}/K_{\rm {m}}} and k c a t {\displaystyle k_{\rm {cat}}} are about 10 5 s − 1 M − 1 {\displaystyle 10^{5}{\rm {s}}^{-1}{\rm {M}}^{-1}} and 10 s − 1 {\displaystyle 10{\rm {s}}^{-1}} , respectively. Michaelis–Menten kinetics relies on

3995-502: The body de novo and closely related compounds (vitamins) must be acquired from the diet. The chemical groups carried include: Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes. For example, about 1000 enzymes are known to use the coenzyme NADH. Coenzymes are usually continuously regenerated and their concentrations maintained at

4080-471: The chemical equilibrium of the reaction. In the presence of an enzyme, the reaction runs in the same direction as it would without the enzyme, just more quickly. For example, carbonic anhydrase catalyzes its reaction in either direction depending on the concentration of its reactants: The rate of a reaction is dependent on the activation energy needed to form the transition state which then decays into products. Enzymes increase reaction rates by lowering

4165-425: The conversion of starch to sugars by plant extracts and saliva were known but the mechanisms by which these occurred had not been identified. French chemist Anselme Payen was the first to discover an enzyme, diastase , in 1833. A few decades later, when studying the fermentation of sugar to alcohol by yeast , Louis Pasteur concluded that this fermentation was caused by a vital force contained within

4250-426: The crystal lattice leaves it unchanged. All crystals have translational symmetry in three directions, but some have other symmetry elements as well. For example, rotating the crystal 180° about a certain axis may result in an atomic configuration that is identical to the original configuration; the crystal has twofold rotational symmetry about this axis. In addition to rotational symmetry, a crystal may have symmetry in

4335-444: The decades since ribozymes' discovery in 1980–1982, the word enzyme alone often means the protein type specifically (as is used in this article). An enzyme's specificity comes from its unique three-dimensional structure . Like all catalysts, enzymes increase the reaction rate by lowering its activation energy . Some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example

SECTION 50

#1732852696063

4420-433: The energy of the transition state. First, binding forms a low energy enzyme-substrate complex (ES). Second, the enzyme stabilises the transition state such that it requires less energy to achieve compared to the uncatalyzed reaction (ES ). Finally the enzyme-product complex (EP) dissociates to release the products. Enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive"

4505-587: The enzyme urease was a pure protein and crystallized it; he did likewise for the enzyme catalase in 1937. The conclusion that pure proteins can be enzymes was definitively demonstrated by John Howard Northrop and Wendell Meredith Stanley , who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin . These three scientists were awarded the 1946 Nobel Prize in Chemistry. The discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography . This

4590-483: The enzyme at the same time. Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, the drug methotrexate is a competitive inhibitor of the enzyme dihydrofolate reductase , which catalyzes the reduction of dihydrofolate to tetrahydrofolate. The similarity between the structures of dihydrofolate and this drug are shown in the accompanying figure. This type of inhibition can be overcome with high substrate concentration. In some cases,

4675-422: The enzyme converts the substrates into different molecules known as products . Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called enzymology and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost

4760-403: The enzyme. As a result, the substrate does not simply bind to a rigid active site; the amino acid side-chains that make up the active site are molded into the precise positions that enable the enzyme to perform its catalytic function. In some cases, such as glycosidases , the substrate molecule also changes shape slightly as it enters the active site. The active site continues to change until

4845-427: The enzyme. For example, the enzyme can be soluble and upon activation bind to a lipid in the plasma membrane and then act upon molecules in the plasma membrane. Allosteric sites are pockets on the enzyme, distinct from the active site, that bind to molecules in the cellular environment. These molecules then cause a change in the conformation or dynamics of the enzyme that is transduced to the active site and thus affects

4930-424: The following series: This arrangement of atoms in a crystal structure is known as hexagonal close packing (hcp) . If, however, all three planes are staggered relative to each other and it is not until the fourth layer is positioned directly over plane A that the sequence is repeated, then the following sequence arises: This type of structural arrangement is known as cubic close packing (ccp) . The unit cell of

5015-437: The form of mirror planes, and also the so-called compound symmetries, which are a combination of translation and rotation or mirror symmetries. A full classification of a crystal is achieved when all inherent symmetries of the crystal are identified. Lattice systems are a grouping of crystal structures according to the point groups of their lattice. All crystals fall into one of seven lattice systems. They are related to, but not

5100-506: The inhibitor can bind to a site other than the binding-site of the usual substrate and exert an allosteric effect to change the shape of the usual binding-site. Crystal structure The smallest group of particles in material that constitutes this repeating pattern is unit cell of the structure. The unit cell completely reflects symmetry and structure of the entire crystal, which is built up by repetitive translation of unit cell along its principal axes. The translation vectors define

5185-461: The lengths of the cell edges ( a , b , c ) and the angles between them (α, β, γ). The positions of particles inside the unit cell are described by the fractional coordinates ( x i , y i , z i ) along the cell edges, measured from a reference point. It is thus only necessary to report the coordinates of a smallest asymmetric subset of particles, called the crystallographic asymmetric unit. The asymmetric unit may be chosen so that it occupies

SECTION 60

#1732852696063

5270-437: The lysosomal compartment. Within the lysosome it remains associated with the membrane, where it binds and degrades its substrate glucocerebroside (GluCer). It requires the activating protein Saposin C as well as negatively charged lipids for maximal catalytic activity. The role of Saposin C is not known; however, it is shown to bind both the lysosomal membrane and the lipid moieties of GluCer, and therefore may recruit GluCer to

5355-468: The mixture. He named the enzyme that brought about the fermentation of sucrose " zymase ". In 1907, he received the Nobel Prize in Chemistry for "his discovery of cell-free fermentation". Following Buchner's example, enzymes are usually named according to the reaction they carry out: the suffix -ase is combined with the name of the substrate (e.g., lactase is the enzyme that cleaves lactose ) or to

5440-429: The nodes of Bravais lattice . The lengths of principal axes/edges, of unit cell and angles between them are lattice constants , also called lattice parameters or cell parameters . The symmetry properties of crystal are described by the concept of space groups . All possible symmetric arrangements of particles in three-dimensional space may be described by 230 space groups. The crystal structure and symmetry play

5525-528: The precise orientation and dynamics of the active site. In some enzymes, no amino acids are directly involved in catalysis; instead, the enzyme contains sites to bind and orient catalytic cofactors . Enzyme structures may also contain allosteric sites where the binding of a small molecule causes a conformational change that increases or decreases activity. A small number of RNA -based biological catalysts called ribozymes exist, which again can act alone or in complex with proteins. The most common of these

5610-411: The primitive lattice vectors are not orthogonal. However, in these cases the Miller indices are conventionally defined relative to the lattice vectors of the cubic supercell and hence are again simply the Cartesian directions . The spacing d between adjacent ( hkℓ ) lattice planes is given by: The defining property of a crystal is its inherent symmetry. Performing certain symmetry operations on

5695-406: The reaction and releases the product. This work was further developed by G. E. Briggs and J. B. S. Haldane , who derived kinetic equations that are still widely used today. Enzyme rates depend on solution conditions and substrate concentration . To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation

5780-733: The reaction rate of the enzyme. In this way, allosteric interactions can either inhibit or activate enzymes. Allosteric interactions with metabolites upstream or downstream in an enzyme's metabolic pathway cause feedback regulation, altering the activity of the enzyme according to the flux through the rest of the pathway. Some enzymes do not need additional components to show full activity. Others require non-protein molecules called cofactors to be bound for activity. Cofactors can be either inorganic (e.g., metal ions and iron–sulfur clusters ) or organic compounds (e.g., flavin and heme ). These cofactors serve many purposes; for instance, metal ions can help in stabilizing nucleophilic species within

5865-482: The same as the seven crystal systems . aP mP mS oP oS oI oF tP tI hR hP cP cI cF The most symmetric, the cubic or isometric system, has the symmetry of a cube , that is, it exhibits four threefold rotational axes oriented at 109.5° (the tetrahedral angle ) with respect to each other. These threefold axes lie along the body diagonals of the cube. The other six lattice systems, are hexagonal , tetragonal , rhombohedral (often confused with

5950-410: The same enzymatic activity have been called non-homologous isofunctional enzymes . Horizontal gene transfer may spread these genes to unrelated species, especially bacteria where they can replace endogenous genes of the same function, leading to hon-homologous gene displacement. Enzymes are generally globular proteins , acting alone or in larger complexes . The sequence of the amino acids specifies

6035-520: The same group of atoms, the basis , positioned around each and every lattice point. This group of atoms therefore repeats indefinitely in three dimensions according to the arrangement of one of the Bravais lattices. The characteristic rotation and mirror symmetries of the unit cell is described by its crystallographic point group . A crystal system is a set of point groups in which the point groups themselves and their corresponding space groups are assigned to

6120-401: The seven crystal systems. In addition to the operations of the point group, the space group of the crystal structure contains translational symmetry operations. These include: There are 230 distinct space groups. By considering the arrangement of atoms relative to each other, their coordination numbers, interatomic distances, types of bonding, etc., it is possible to form a general view of

6205-424: The smallest physical space, which means that not all particles need to be physically located inside the boundaries given by the lattice parameters. All other particles of the unit cell are generated by the symmetry operations that characterize the symmetry of the unit cell. The collection of symmetry operations of the unit cell is expressed formally as the space group of the crystal structure. Vectors and planes in

6290-412: The structure which in turn determines the catalytic activity of the enzyme. Although structure determines function, a novel enzymatic activity cannot yet be predicted from structure alone. Enzyme structures unfold ( denature ) when heated or exposed to chemical denaturants and this disruption to the structure typically causes a loss of activity. Enzyme denaturation is normally linked to temperatures above

6375-447: The structures and alternative ways of visualizing them. The principles involved can be understood by considering the most efficient way of packing together equal-sized spheres and stacking close-packed atomic planes in three dimensions. For example, if plane A lies beneath plane B, there are two possible ways of placing an additional atom on top of layer B. If an additional layer were placed directly over plane A, this would give rise to

6460-519: The substrate is completely bound, at which point the final shape and charge distribution is determined. Induced fit may enhance the fidelity of molecular recognition in the presence of competition and noise via the conformational proofreading mechanism. Enzymes can accelerate reactions in several ways, all of which lower the activation energy (ΔG , Gibbs free energy ) Enzymes may use several of these mechanisms simultaneously. For example, proteases such as trypsin perform covalent catalysis using

6545-405: The substrates. Enzymes can therefore distinguish between very similar substrate molecules to be chemoselective , regioselective and stereospecific . Some of the enzymes showing the highest specificity and accuracy are involved in the copying and expression of the genome . Some of these enzymes have " proof-reading " mechanisms. Here, an enzyme such as DNA polymerase catalyzes a reaction in

6630-399: The synthesis of antibiotics . Some household products use enzymes to speed up chemical reactions: enzymes in biological washing powders break down protein, starch or fat stains on clothes, and enzymes in meat tenderizer break down proteins into smaller molecules, making the meat easier to chew. By the late 17th and early 18th centuries, the digestion of meat by stomach secretions and

6715-438: The type of reaction (e.g., DNA polymerase forms DNA polymers). The biochemical identity of enzymes was still unknown in the early 1900s. Many scientists observed that enzymatic activity was associated with proteins, but others (such as Nobel laureate Richard Willstätter ) argued that proteins were merely carriers for the true enzymes and that proteins per se were incapable of catalysis. In 1926, James B. Sumner showed that

6800-493: The unit cell (in the basis of the lattice vectors). If one or more of the indices is zero, it means that the planes do not intersect that axis (i.e., the intercept is "at infinity"). A plane containing a coordinate axis is translated so that it no longer contains that axis before its Miller indices are determined. The Miller indices for a plane are integers with no common factors. Negative indices are indicated with horizontal bars, as in (1 2 3). In an orthogonal coordinate system for

6885-486: The yeast cells called "ferments", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells." In 1877, German physiologist Wilhelm Kühne (1837–1900) first used the term enzyme , which comes from Ancient Greek ἔνζυμον (énzymon)  ' leavened , in yeast', to describe this process. The word enzyme

6970-781: Was a version of glucocerebrosidase that was harvested from human placental tissue and then modified with enzymes. It was approved by the FDA in 1991 but has been withdrawn from the market due to the approval of similar drugs made with recombinant DNA technology instead of being harvested from tissue. Drugs made recombinantly pose no risk of diseases being transmitted from the tissue used in harvesting, and are less expensive to manufacture. Recombinant glucocerebrosidases used as drugs include: Enzyme Enzymes ( / ˈ ɛ n z aɪ m z / ) are proteins that act as biological catalysts by accelerating chemical reactions . The molecules upon which enzymes may act are called substrates , and

7055-581: Was first done for lysozyme , an enzyme found in tears, saliva and egg whites that digests the coating of some bacteria; the structure was solved by a group led by David Chilton Phillips and published in 1965. This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail. Enzymes can be classified by two main criteria: either amino acid sequence similarity (and thus evolutionary relationship) or enzymatic activity. Enzyme activity . An enzyme's name

7140-444: Was shown to bind GCase and facilitate transport to the lysosome, demonstrating a mechanism for M6P-independent lysosomal trafficking. This conclusion was called into question when a crystal structure of GCase in complex with LIMP-2 showed a Mannose 6-phosphate moiety on LIMP-2, suggesting the complex can also follow the traditional mannose-6-phosphate pathway . Mutations in the glucocerebrosidase gene cause Gaucher's disease ,

7225-451: Was used later to refer to nonliving substances such as pepsin , and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897. In a series of experiments at the University of Berlin , he found that sugar was fermented by yeast extracts even when there were no living yeast cells in

#62937