Approaches to deorphanization of human and microbial cytochrome P450 enzymes.
One of the general problems in biology today is that we are characterizing genomic sequences much faster than identifying the functions of the gene products, and the same problem exists with cytochromes P450 (P450). One fourth of the human P450s are not well-characterized and therefore considered "orphans." A number of approaches to deorphanization are discussed generally. Several liquid chromatography-mass spectrometry approaches have been applied to some of the human and Streptomyces coelicolor P450s. One current limitation is that too many fatty acid oxidations have been identified and we are probably missing more relevant substrates, possibly due to limits of sensitivity.
Guengerich
F Peter
FP
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. f.guengerich@vanderbilt.edu
Tang
Zhongmei
Z
Cheng
Qian
Q
Salamanca-Pinzón
S Giovanna
SG
D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D005810:Multigene Family; D048372:Streptomyces coelicolor / Q000201:enzymology* / Q000378:metabolism; D013379:Substrate Specificity
D001426:Bacterial Proteins; D002273:Carcinogens; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System