The Cytochrome P450 Engineering Database: integration of biochemical properties

Demet Sirim,Florian Wagner,Andrey Lisitsa,Jürgen Pleiss

doi:10.1186/1471-2091-10-27

Demet Sirim, Florian Wagner + Show 2 more

Open Access

https://doi.org/10.1186/1471-2091-10-27

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Abstract

BackgroundCytochrome P450 monooxygenases (CYPs) form a vast and diverse enzyme class of particular interest in drug development and a high biotechnological potential. Although very diverse in sequence, they share a common structural fold. For the comprehensive and systematic comparison of protein sequences and structures the Cytochrome P450 Engineering Database (CYPED) was established. It was built up based on an extensible data model that enables its functions readily enhanced.DescriptionThe new version of the CYPED contains information on sequences and structures of 8613 and 47 proteins, respectively, which strictly follow Nelson's classification rules for homologous families and superfamilies. To gain biochemical information on substrates and inhibitors, the CYPED was linked to the Cytochrome P450 Knowledgebase (CPK). To overcome differences in the data model and inconsistencies in the content of CYPED and CPK, a metric was established based on sequence similarity to link protein sequences as primary keys. In addition, the annotation of structurally and functionally relevant residues was extended by a reliable prediction of conserved secondary structure elements and by information on the effect of single nucleotide polymorphisms.ConclusionThe online accessible version of the CYPED at http://www.cyped.uni-stuttgart.de provides a valuable tool for the analysis of sequences, structures and their relationships to biochemical properties.

Highlights

Cytochrome P450 monooxygenases (CYPs) form a vast and diverse enzyme class of particular interest in drug development and a high biotechnological potential
To gain biochemical information on substrates and inhibitors, the Cytochrome P450 Engineering Database (CYPED) was linked to the Cytochrome P450 Knowledgebase (CPK)
The online accessible version of the CYPED at http://www.cyped.uni-stuttgart.de provides a valuable tool for the analysis of sequences, structures and their relationships to biochemical properties

Summary

Background

Cytochrome P450 monooxygenases (CYPs) constitute one of the largest superfamilies of enzymes, spread widely among species of microorganisms, plants, animals, and humans. 218 proteins without CYP name information and no sequence similarity to existing families, as well as 279 protein fragments were discarded Following this procedure the entries of the CYPED are consistent with the recommendations of the nomenclature committee. Information on human CYP alleles was extracted from the "Home Page of the Human Cytochrome P450 (CYP) Allele Nomenclature Committee" [15] and stored in tables designated for this purpose in the database The mutations and their effect, whether the enzymes lack of activity or gained increased activity, are listed on the protein feature page. 3575 CYPED proteins matched the respective CPK entries with a sequence identity of more than 90% These matches provided the links to 3257 different compounds (1699 substrates, 723 inducers and 1227 inhibitors). For each homologous family and superfamily, family specific HMM profiles http:// hmmer.janelia.org/ are supplied

Utility and discussion

Conclusion

Montellano Od

Nelson DR

Findings

16. Mestres J