Enzyme Structure Database

The ENZYME database at http //www.expasy.ch/enzyme/ provides information on EC number, name, catalytic activity, and hyperlinks to sequence data of enzymes. The 3D structures of enzymes can be accessed via Enzyme Structures Database at http //www.biochem.ucl.ac.uk/bsm/enzyme/index.html. Some other enzyme databases are listed in Table 7.1. 

Enzyme structure database Structures http //www.biochem.ucl.ac.uk/bsm/enzyme/index.html... 

Figure 7.7. Home page of enzyme structure database. Links to enzyme structure and analysis servers are available at the Enzyme Structure Database which extracts and collects enzyme structures from pdb files.

Figure 7.8. The substrate interaction at the active site of an enzyme. The interaction of tetra-A/,A/,A/,A/-acetylchitotetraose (NAG4) with amino acid residues at the active site of lysozyme (ILZC.pdb) can be viewed/saved at PDBsum server (Enyme Structure Database->PDBsum->LIGPLOT of interactions under Ligand) linked to the Enzyme Structure Database.

Search the Enzyme Structure Database for y-chymotrypsin active site (by the aid of the active-site-modified enzyme or active-site-specific inhibitor-enzyme complex) to identify and depict (save pdb file) the catalytic triad of y-chymotrypsin. 

Enzyme Commission, EC ENZYME database Enzyme Structures Database Esther Esterases G6P dehydrogenase Leonora Enzyme kinetics LIGAND... 

Of the 14500 entries currently in PDB, there are roughly 7200 enzyme structures. The Enzymes Structures Database, maintained by University College, University of London, focuses on this portion of PDB and offers links between the E.C. nomenclature of the IUBMB and the corresponding PDB entries. 

DIPPR Pure Compound Database Dortmund Data Bank Enzyme Nomenclature Database Enzyme Structures Database European Bioinformatics Institute... 

Fig. 34. Glu-72- Zn interactions in native carboxypeptidase A and in carboxypep-tidase A-inhibitor complexes (inhibitors have been reviewed by Christianson and Lipscomb, 1989). When substrates or inhibitors bind to the enzyme active site and interact with the zinc ion, the interaction of the metal with Glu-72 tends from bidentate toward uniden-tate coordination. The flexibility of protein-zinc coordination may be an important aspect of catalysis in this system, and the Glu-72->Zn - coordination stereochemistry observed here is consistent with the stereochemical analysis of carboxylate-zinc interactions from the Cambridge Structural Database (Carrell et al., 1988 see Fig. 4).

Structural Database of Neutral Lipases and Related Enzymes... 

Now that the principles of enzymatic architecture and the corresponding analysis strategies have been highlighted and briefly discussed, an overview of the existing enzyme classes and their properties is needed. Given the more than 4000 different enzyme types, any attempt at only listing them would be far beyond the scope of this chapter. Fortunately, there are a number of specialized databases available, which aim to treat various aspects of enzyme structure and function comprehensively. All of these databases are accessible via the Internet, and a list of the relevant URL addresses is given in Table 5-1. 

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. 

Although not being in the focus of this chapter, structural databases are a most useful resource for the scientist interested in enzymes and reaction mechanisms. The Protein Data Bank (PDB) is the main repository for all three-dimensional structures of macromolecules including enzymes 55. Nowadays, most journals accepting manuscripts that describe new structures require a simultaneous deposition of the structural coordinates with the PDB database. In addition to the structure of single protein molecules, the PDB also contains several entries of multi-protein complexes, or proteins bound to small-molecule compounds. 

Step 2 amd Step 3. Chemical structures of the substrates, cofactors, and inhibitors of the enzymes listed in Step 1 are searched for in the Enzyme-Reaction database (see the next section) by the entry codes of these enzymes. 

Two copies of the Enzyme-Reaction database are prepared one copy Is accessible through the FORTRAN 77 programs for lead-structure findings discussed in the above section and the other Is on a FACOM relational-database system. 

The complete LFMM force field has been implemented in the molecular operating environment (MOE) as an extension named DommiMOE (d orbital molecular mechanics in MOE) [28]. LFMM has been applied extensively to copper complexes, from simple Cu(II) amines [29] to copper enzymes [32], and a variety of force field parameters for copper complexes are available. The parametrization is done by fitting the parameters in (4) to the crystallographic stracture data provided by the Cambridge Structural Database [29, 30], while DFT calculation results are sometimes also involved in the fitting [32]. 

Fig. 6.26 Multiple overlay of baeterial eytochrome P450 struetures. An overlay of baeterial P450 structures reveals large variability. A stereo-view is presented for the struetural alignments of all the P450 enzyme structures from Mycobacterium tuberculosis present in the database, together with those of the three model microbial P450s shown in Fig. 6.2 (P450s EryF, BM3, and Cam). Color...

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