BRENDA database

Table 8.1 Summary of kinetic constants for the enzymes featured in Section 8.1 of Chapter 8. ALL the data are obtained from the enzyme database - BRENDA (http //www.brenda-enzymes.info/) except where indicated (a) vaLue of k n/Kn estimated assuming aLL substrate added in buffer is avaiLabLe to enzyme i.e., has not been sequestered as acetaL or ketaL derivatives, as appropriate) (b) kcat data from FieLds et aL, 2006 (c) /feat data from rat source (d) kinetic data from Masaki et ai, 2001 (e) /Ccat data from Day and Shaw, 1992 (f) kinetic data from bovine source (g) kinetic data from human source (h) aLL kinetic data from Wright et ai, 2006. Abbreviations GAP 3-gLyceraLdehyde 3-phosphate DHAP dihydroxyacetone phosphate OAA oxaLoacetate NADH reduced nicotinamide adenine dinucLeotide chloramp chLoramphenicoL thio-ACh thio acetyLchoLine. Roman numeraL denote compounds iLLustrated in the set of structures accompanying this tabLe. 

Biological Macromolecule Crystallization xpdb.nist.gov 8060/BMCD4/index.faces Database BRENDA... 

BRENDA database, Jnne 2006 (http //www.brenda.uni-koeln.de). 

BRENDA [191,192] The BRaunschweig ENzyme DAtabase http //www.brenda enzymes.info/... 

J. Barthelmes, C. Ebeling, A. Chang, I. Schomburg, and D. Schomburg, Brenda, amenda and frenda The enzyme information system in 2007. Nucleic Acids Res. 35(Database issue), D511 D514 (2007). 

Schomburg I, Chang A, Ebehng C, et al. (2004) BRENDA, the enzyme database Updates and major new developments. Nucl. Acids Res. 32 D431-D433. http //www.brenda.uni-koeln.de/. 

An overview of databases yields the number of publicly accessible genomes 112 finished microbial and two eukaryotic genomes with over 300 overall in progress (as of April 2003). The number of enzymes with E.C. nomenclature is 4159 according to the ExPASy website and 3225 according to Brenda databases the number of accessible 3D structures totals 20 946, 18 872 of which are proteins. 

Search the BRENDA database and find information on the enzymes EC 1.13.12.14, azobenzene reductase, and nitrogenase. What reactions do those enzymes catalyze What are their optimum p H and temperature operating ranges And what are their typical TOFs ... 

Figure 7.5. Search enzyme information at Brenda. Brenda is the comprehensive enzyme database for retrieving chemical, kinetic, and structural properties of enzymes via EC number, enzyme name, and organism (biological source). The search page by EC number is shown.

Prior to the start of any experimental substrate finding activity, databases should be mined. A tremendous amount of information about proteases, substrates, inhibitors, and structures can be retrieved from two searchable databases MEROPS (Rawlings et al., 2006) (http //merops.sanger. ac.uk) and BRENDA (www.brenda-enzymes.de), that serve as good starting points for assay development in many cases. These databases are available to the public and should be consulted as primary sources of information. 

Coenzyme A (CoA) is a cofactor that has been estimated to be used by about 4% of all enzymes, although more recent analysis of the BRENDA database (http //www.brenda.uni-koeln.de/) suggests the number may be closer to 9% (1). The biochemical pathways and processes involving CoA thioesters are diverse and widespread, whereas the kinds of reactions involved primarily follow the inherent reactivity of the thioester functionality. This article provides a brief overview of CoA biosynthesis and a summary of the common types of reactions of CoA thioesters. Also presented is a brief introduction to structural studies and a more extensive description of some types of analogs of natural CoA thioesters that have been employed as mechanistic probes for CoA using enzymes. The application of CoA derivatives and CoA biosynthetic enzymes for the tagging of carrier proteins and carrier protein fusions is also described. 

Several databases for metabolic pathways are available currently from the Internet, and some major representatives are listed in Table 1. KEGG (Bioinformatics Center, Institute for Chemical Research, Kyoto University, Kyoto, Japan), BRENDA (Institute... 

MichaeUs-Menten (MM) kinetics, although not perfect and in many cases inadequate for a number of reasons, have been used widely to describe the dynamics of catalysis of most enzymes. Databases such as BRENDA [5], containing sets of MM kinetic constants for most enzymes in a wide array of organisms, are widely available. The basic MM equation (Fig. 7-2) is derived for a simple system as shown ... 

Databases such as Enzyme [12], Brenda [5], Ligand [28] and EMP [6] contain enzymes which are involved in a large number of reactions. Each enzyme with known enzyme function are catalogued and named by a nomenclature committee. Also included in the databases is information on the reaction and specificity of the enzyme and the various conditions the enzyme will be active under. Information about the structure and stability of the enzyme and the preparation of the reaction may also be included. 

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. 

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD) is a data repository providing curated information on microbial catabolic enzymes and their organization into metabolic pathways 54. At present, the UM-BBD stores information on approximately 100 pathways with 700 reactions, 600 compounds and 400 enzymes. The database does not try to cover every known enzyme but rather focuses on those used for the biodegradation of xenobiotics. UM-BBD is linked to the ENZYME, BRENDA and KEGG/LIGAND databases mentioned above. 

The development of the enzyme data information system BRENDA was started in 1987 at the German National Research Centre for Biotechnology in Braunschweig (GBF) and is now continmng at the Technical University Braunschweig, Institute of Bioinformatics Systems Biology. The present book Springer Handbook of Enzymes represents the printed version of this data bank. The information system has been developed into a full metabolic database. 

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. 

For each reaction in the generated pathway, users can manually select the reactions to be represented by dynamic equations. InitiaUy, the GEM system would automatically search for static reactions based on monomer enzymes found in Brenda and Swiss-PROT databases. Based on the search results, the static part of the model is then generated using the hybrid dynamic/static simulation algorithm detailed below. Finally, the generated pathway model can be used for simulations in E-Ccll System. Users can then specify dynamic equations by selecting an appropriate reaction mechanism and input reaction parameters, or they can program their own set of reaction process description files. 

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