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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
An expanded, unified substrate recognition site map for mammalian cytochrome P450s: Analysis of molecular interactions between 15 mammalian CYP450 isoforms and 868 substrates
Current Drug Metabolism, Volume 12, No. 7, Year 2011
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Description
The original map of mammalian cytochrome P450 (CYP450) residues involved in substrate recognition was prepared for the CYP2 family by Gotoh in 1992 by manual alignment of mammalian CYP450 residues with substrate recognition site (SRS) residues manually delimited from a bacterial cytochrome P450-substrate complex. Using modern structural bioinformatics tools, we have identified CYP450-ligand interactions in mammalian complexes to create a "X-ray structures" SRS map. In a parallel approach, we have built a "docking" SRS map by successful docking of 868 known substrates of 10 mammalian CYP450 isoforms and analysis of contacts made in docking solutions. We subsequently combined these maps to create a unified description of SRSs. The new map largely agrees with the original map by Gotoh with the six original SRS regions appearing in similar locations along the CYP450 sequence as in Gotoh's map. However, important differences also occur: Two new SRS regions appear before SRS1 and we have assigned them as SRS1'a and SRS1'b; SRS1 is much bigger in our map than in Gotoh's (49 aligned positions versus 28); & SRS2 and SRS3 are co-joined in our map to give a single large SRS region (60 aligned positions) we have designated as SRS(2,3), in contrast to the 9 and 10 aligned positions individually covered by SRS2 and SRS3 respectively in Gotoh's original map. These differences result in the SRS zone covering 33 % of the mammalian CYP450 sequence in our map as opposed to 16 % in Gotoh's map. © 2011 Bentham Science Publishers © 2011 Bentham Science Publishers.
Authors & Co-Authors
Zawaira, Alexander
South Africa, Pretoria
The Council for Scientific and Industrial Research
Lim, Chingching
South Africa, Cape Town
University of Cape Town
Coulson, Lauren
Singapore, Singapore City
National University of Singapore
Blackburn, Jonathan M.
Singapore, Singapore City
National University of Singapore
Yap, Chun Wei
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 21
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.2174/138920011796504554
ISSN:
13892002
e-ISSN:
18755453