Abstract：
:A novel cytochrome P450, CYP53A15, was identified in the pathogenic filamentous ascomycete Cochliobolus lunatus. The protein, classified into the CYP53 family, was capable of para hydroxylation of benzoate. Benzoate is a key intermediate in the metabolism of aromatic compounds in fungi and yet basically toxic to the organism. To guide functional analyses, protein structure was predicted by homology modeling. Since many naturally occurring antifungal phenolic compounds are structurally similar to CYP53A15 substrates, we tested their putative binding into the active site of CYP53A15. Some of these compounds inhibited CYP53A15. Increased antifungal activity was observed when tested in the presence of benzoate. Some results suggest that CYP53A15 O-demethylation activity is important in detoxification of other antifungal substances. With the design of potent inhibitors, CYP53 enzymes could serve as alternative antifungal drug targets.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Podobnik B,Stojan J,Lah L,Krasevec N,Seliskar M,Rizner TL,Rozman D,Komel Rdoi
10.1021/jm800030esubject
Has Abstractpub_date
2008-06-26 00:00:00pages
3480-6issue
12eissn
0022-2623issn
1520-4804journal_volume
51pub_type
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