Cofactors classification

Metal ions, effect of size, 200-205 Metalloenzymes, see also Enzyme cofactors classification of, by cofactor and coupled general base, 205-207, 206 electrostatic interactions in, 205-207 SNase, 189-197... 

Protein sequence homology suggests that sulfite oxidase and assimilatory nitrate reductase are members of the same molybdenum enzyme subfamily [31]. Consistent with this classification, the cofactors of sulfite oxidase and assimilatory nitrate reductase differ significantly from those in dmso reductase, aldehyde oxido-reductase, xanthine oxidase (see Section IV.E.), and even respiratory nitrate reductase (Section IV.D). The EXAFS of both sulfite oxidase [132-136] and assimilatory nitrate reductase [131,137,138] and x-ray studies of sulfite oxidase (chicken liver) [116] confirm that the molybdenum center is coordinated by two sulfur atoms from a single MPT ligand and by the sulfur atom of a cysteine side chain. The Movl state is bis(oxido) coordinated (Figure 14). 

During natural evolution, a broad variety of enzymes has been developed, which are classified according to the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (IUBMB). Thus, for each type of characterized enzyme an EC (Enzyme Commission) number has been provided (see http // www.expasy.ch/enzyme/). For instance, all hydrolases have EC number 3 and further subdivisions are provided by three additional digits, e.g. all lipases (official name triacylglycerol lipases) have the EC number 3.1.1.3 and are thus distinguished from esterases (official name carboxyl esterases) having the EC number 3.1.1.1. This classification is based on the substrate (and cofactor) specificity of an enzyme only, however often very similar amino acid sequences and also related three-dimensional structures can be observed. 

Flavoenzymes constitute about 2% of all biological catalysts and are classified in several ways. One classification is based on EC number (enzyme nomenclature) and refers to the type of reaction catalyzed. More sophisticated classifications concern the inclusion of sequence, fold, and function. Historically, a distinction is made between simple and complex flavoenzymes (4). The latter proteins contain besides flavin other cofactors like heme, tetrahydrobiopterin, and metal ions. 

Reaction specificity is the most significant and most widespread classification of enzymes (Tab. 3.10). Another way of classifying enzymes is by their complexity (Tab. 3.11). As already pointed out, enzymes are proteins or at least consist predominantly of a protein portion. Some enzymes need cofactors (prosthetic groups or cosubstrates see Tab. 3.11). 

Reflecting the lack of in-depth experimental data available at this time, even the classiflcation of metal-dependent enzymes was notably nonsystematic. In an early review, five categories were set forth heme, copper-containing, proteolytic, carbonic anhydrase, and phosphatase . A later classification" was made according to the types of reactions catalyzed electron transfer or redox (Cu, Fe, Mo), group transfer (Mg, Mn), decarboxylations and hydrolyses (Mn, Zn), and binding of pyridine nucleotide cofactors (Zn). 

The ENZYME database1501, maintained by the Swiss Institute for Bioinformatics (SIB), provides a comprehensive list of all IUBMB classifications, together with associated information such as systematic and alternative enzyme names, cofactor requirements, and pointers to the corresponding entry in the SWISS-PROT database of protein sequences1511. In addition, there is a concise free-text description of the reaction catalyzed, together with a description of preferential substrates and products. Currently, the ENZYME database holds entries for approximately 3700 enzymes. 

A much more ambitious database that builds on the IUBMB classification is BRENDA, maintained by the Institute of Biochemistry at the University of Cologne. In addition to the data provided by the ENZYME database, the BRENDA curators have extracted a large body of information from the enzyme literature and incorporated it into the database. The database format strives to be readable by both humans and machines. The categories of data stored in BRENDA comprise the EC-number, systematic and recommended names, synonyms, CAS-registry numbers, the reaction catalyzed, a list of known substrates and products, the natural substrates, specific activities, KM values, pH and temperature optima, cofactor and ion requirements, inhibitors, sources, localization, purification schemes, molecular weight, subunit structure, posttranslational modifications, enzyme stability, database links, and last but not least an extensive bibliography. Currently, BRENDA holds entries for approximately 3500 different enzymes. 

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