TY - JOUR
AU - Degtyarenko, Kirill N.
AB - Abstract The Directory of P450-containing Systems on World-Wide Web has been designed to facilitate access to electronic resources for all researchers working in the field of P450-containing and related enzyme systems. Currently, it contains the most up-to-date list of sequences of both the P450 superfamily and proteins mediating electron transfer to P450, i.e. NADPH:P450 reductases, specific NAD(P)H:ferredoxin reductases, cytochrome b5 reductases, ferredoxins and cytochromes b5, and their homologues. All the referenced sequences are provided with accession numbers and links to major sequence databanks: PIR, SWISS-PROT, EMBL/GenBank and PRF. An associated database of steroid substrates and products of P450-dependent reactions has also been developed. Background P450 enzymes constitute a superfamily of haem-thiolate proteins (1) which are involved in the metabolism of a plethora of both exogenous and endogenous compounds (2,3). P450s are widely distributed in animals, fungi, plants and eubacteria; recently, a potential P450 sequence from the archaeobacterium Sulfolobus solfataricus has been reported (4). Usually, P450 enzymes act as terminal oxidases in multicomponent electron transfer chains, termed P450-containing monooxygenase systems (5). All known P450-containing systems share a common structural and functional domain architecture. Apart from P450 itself, these systems can comprise several fundamentally different protein components and domains, all of which are also shared by other multicomponent/ multidomain enzyme systems with various functions (5). The rapid growth of sequence information is making the gathering together of a comprehensive and up-to-date data set for extensive protein families increasingly laborious. In an effort to facilitate access to electronic resources for all researchers working in the field of P450 proteins and P450-containing systems, a WorldWide Web server called the Directory of P450-containing Systems (DPS) was established in August 1994 (6). Contents The home page of DPS (Fig. 1) provides access to all associated hypertext documents. Figure 1 View largeDownload slide The DPS home page. This page gives access to entry points to all associated hypertext documents. Figure 1 View largeDownload slide The DPS home page. This page gives access to entry points to all associated hypertext documents. Table 1 View largeDownload slide Contents of DPS ‘core’ Table 1 View largeDownload slide Contents of DPS ‘core’ Components of P450-containing systems The ‘core’ of DPS is systematic information on protein and nucleic acid sequences of the P450 superfamily as well as other components of P450-containing systems and their homologues. A typical DPS entry is shown in Figure 2. It contains accession numbers for known sequences of relevant proteins in PIR (7), SWISS-PROT (8), EMBL (9) and PRF/SEQDB (10) databases. Only complete or reasonably complete sequences are being referenced in DPS; as a rule, ESTs are not considered. All the accession numbers are linked to the corresponding databases: ‘clicking’ the code retrieves the sequence. This allows the user to get the most up-to-date versions of sequences as soon as they appear in major databases. The search for new sequences is conducted automatically by a perl script (see reference 6 for more details). In addition, DPS has links to other databases such as PROSITE (11), PRINTS (12), BLOCKS (13), ProDom (14), Prot-Fam at MIPS (7), Entrez Taxonomy Database at NCBI (15), ENZYME (16), LIGAND (17) and OMIM (18). The tables of P450 sequences are being continuously updated in accordance with the P450 nomenclature recommendations (19). As of September 1, 1996 DPS contained reference data on 927 genes from 256 different species (Table 1). A special page is dedicated to genes with a known exon/intron structure. Steroid ligands of P450s The most extended, and possibly evolutionarily most ancient, P450-dependent biotransformation of endogenous substrates concerns the steroids (20). P450 enzymes participate in such key biological pathways as cholesterol biosynthesis, bile acid formation, steroid hormone production and vitamin D metabolism. We have created a database of steroid ligands (substrates and products) of P450s. A typical entry includes general information on a compound (structural and empirical formulae, trivial and systematic names, CAS and Merck Index numbers, and a link to the Klotho chemical compounds database) (21), information on particular P450-dependent reactions [pathway, type of reaction, enzyme name, ENZYME database reference (16), and links to sequences of relevant P450s in SWISS-PROT (8) or EMBL (9) databases], and a bibliography. As of September 1, 1996 the database contained 63 P450 ligand entries. A related database of P450-dependent reactions is under construction. A sample entry is presented in Figure 3. Apart from the information on the given reaction, which is identical to that in cross-linked entries of the steroid ligand database, it includes the graphical representation of a reaction and a list of all the pathways involved. Selected references on P450-containing systems This section contains pertinent bibliographical information organized in 32 files. Most of the literature references have links to Entrez-MEDLINE abstracts at NCBI (15) and to a number of other on-line resources. Families of structural domains of P450-containing systems This section contains tables and cartoons giving an idea of the organization and relationships of the main structural/functional domains of P450-containing and other enzyme systems. PRINTS entries for structural domains of P450-containing systems For all the components/domains of P450 systems, the corresponding fingerprints have been constructed, which can be used to identify the new members of these protein superfamilies, even if the overall amino acid sequence identities are at or below the limit of significance (6). The fingerprint entries are integrated in the PRINTS database (12). As of July 1, 1996 the PRINTS database contained 14 relevant entries. Figure 2 View largeDownload slide A typical page from DPS. Underlined text indicates the hypertext links to the number of databases. Figure 2 View largeDownload slide A typical page from DPS. Underlined text indicates the hypertext links to the number of databases. Figure 3 View largeDownload slide A sample entry from a database of P450-dependent reactions. Figure 3 View largeDownload slide A sample entry from a database of P450-dependent reactions. OMIM entries related to P450-containing systems MOLSCRIPT images of known 3D structures The names of the two last sections are self-explanatory. The former represents a table containing links to 54 entries of the Online Mendelian Inheritance in Man (OMIM) database (18). The latter provides an interface to drawings produced with the program MOLSCRIPT (22); the images can be retrieved both in PostScript and GIF format. Availability DPS is currently available on the WorldWide Web servers of the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy at and the Agricultural Biotechnology Center, Gödöllö, Hungary at . Acknowledgements This project was launched during the authors' fellowship at the Protein Structure and Function Laboratory of the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy. We are grateful to David R. Nelson of University of Tennessee at Memphis for his assistance with P450 nomenclature. References 1 NC-IUB (Nomenclature Committee of the International Union of Biochemistry), Eur. J. Biochem , 1991, vol. 200 (pg. 599- 611) CrossRef Search ADS PubMed 2 Nebert D.W., Gonzalez F.J.. , Annu. Rev. Biochem. , 1987, vol. 56 (pg. 945- 993) CrossRef Search ADS PubMed 3 Munro A.W., Lindsay J.G.. , Mol. 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Collier H.. , Proceedings of the 1995 International Chemical Informatics Conference, Nimes, France , 1995 UK Infonortics Ltd. Calne, UK(pg. 48- 61) 22 Kraulis P.J.. , J. Appl. Crystallogr. , 1991, vol. 24 (pg. 946- 950) CrossRef Search ADS © 1997 Oxford University Press
TI - The Directory of P450-containing Systems in 1996
JF - Nucleic Acids Research
DO - 10.1093/nar/25.1.274
DA - 1997-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/the-directory-of-p450-containing-systems-in-1996-kBimq3Lmv8
SP - 274
EP - 277
VL - 25
IS - 1
DP - DeepDyve
ER -