Enzyme resource sites

The active-site-directed inhibition of enzymes has been an important research topic in pharmaceutical drug design (Sandler, 1980). An early development of anti-cancer agents involved inhibitions of dihydrofolate reductase and thymidylate synthetase. Search enzyme resource sites for kinetic data (turnover number, Km and Kt) of these two enzymes. 

Thus, the EC numbers provide unique identifiers for enzyme functions, and give us useful keyword entries in database searches (http //www.chem.qmw.ac.uk/iubmb/ enzyme/). Enzyme nomenclature/common names and properties are also available at ENZYME (http //www.expasy.org/enzyme) and BRENDA (http //www.brenda.uni-koeln. de). IntEhz (http //www.ebi.ac.uk/intenzy) is the integrated enzyme database and enzyme nomenclature. Table 11.1 lists some enzyme resource sites providing general information. 

EMP at http //wit.mcs.anl.gov/EMP/ is the resource site for summarized enzyme data that have been published in the literature. The site opens with the Simple query form (Figure 7.6). Enter the enzyme name into the name query box of Find an enzyme, select Common name, then enter the common organism name for In an organism or taxon, and enter tissue name in response to Extracted from. Clicking Submit Query returns an itemized summary of published enzyme data (data from one article may appear in more than one entries for different substrates) including concise assay and purification procedures, kinetic equations and kinetic parameters. 

Quantum chemical methods aim to treat the fundamental quantum mechanics of electronic structure, and so can be used to model chemical reactions. Such quantum chemical methods are more flexible and more generally applicable than molecular mechanics methods, and so are often preferable and can be easier to apply. The major problem with electronic structure calculations on enzymes is presented by the very large computational resources required, which significantly limits the size of the system that can be treated. To overcome this problem, small models of enzyme active sites can be studied in isolation (and perhaps with an approximate model of solvation). Alternatively, a quantum chemical treatment of the enzyme active site can be combined with a molecular mechanics description of the protein and solvent environment the QM/MM approach. Both will be described below. 

In addition to the metabolic databases listed above, some of the enzyme databases described in the previous chapter (Chapter 6) also serve as useful metabolic resources. All of the enzyme and metabolic databases make use of EC (Enzyme Commission) numbers which are available at the International Union of Biochemistry and Molecular Biology (IUBMB) site (http //www.chem.qmw.ac.uk/ iubmb/enzyme/). 

Porter CT, Bartlett GJ, Thornton JM. The catalytic site atlas a resource of catalytic sites and residues identified in enzymes using structural data. Nucleic Acids Res. 2004 32 D129-133. 

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