1q5d
From Proteopedia
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Epothilone B-bound Cytochrome P450epoK
Overview
Epothilones are potential anticancer drugs that stabilize microtubules by, binding to tubulin in a manner similar to paclitaxel. Cytochrome P450epoK, (P450epoK), a heme containing monooxygenase involved in epothilone, biosynthesis in the myxobacterium Sorangium cellulosum, catalyzes the, epoxidation of epothilones C and D into epothilones A and B, respectively., The 2.10-, 1.93-, and 2.65-A crystal structures reported here for the, epothilone D-bound, epothilone B-bound, and substrate-free forms, respectively, are the first crystal structures of an epothilone-binding, protein. Although the substrate for P450epoK is the largest of a P450, whose x-ray structure is known, the structural changes along with, substrate binding or product release are very minor and the overall fold, is similar to other P450s. The epothilones are positioned with the, macrolide ring roughly perpendicular to the heme plane and I helix, and, the thiazole moiety provides key interactions that very likely are, critical in determining substrate specificity. Interestingly, there are, strong parallels between the epothilone/P450epoK and paclitaxel/tubulin, interactions. Based on structural similarities, a plausible epothilone, tubulin-binding mode is proposed.
About this Structure
1Q5D is a Single protein structure of sequence from Sorangium cellulosum with HEM and EPB as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structures of epothilone D-bound, epothilone B-bound, and substrate-free forms of cytochrome P450epoK., Nagano S, Li H, Shimizu H, Nishida C, Ogura H, Ortiz de Montellano PR, Poulos TL, J Biol Chem. 2003 Nov 7;278(45):44886-93. Epub 2003 Aug 21. PMID:12933799
Page seeded by OCA on Wed Nov 21 00:23:43 2007
