1pkf

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{{STRUCTURE_1pkf| PDB=1pkf | SCENE= }}
{{STRUCTURE_1pkf| PDB=1pkf | SCENE= }}
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'''Crystal Structure of Epothilone D-bound Cytochrome P450epoK'''
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===Crystal Structure of Epothilone D-bound Cytochrome P450epoK===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12933799 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12933799}}
==About this Structure==
==About this Structure==
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[[Category: Heme-enzyme]]
[[Category: Heme-enzyme]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:11:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:35:37 2008''

Revision as of 15:35, 27 July 2008

Image:1pkf.png

Template:STRUCTURE 1pkf

Crystal Structure of Epothilone D-bound Cytochrome P450epoK

Template:ABSTRACT PUBMED 12933799

About this Structure

1PKF is a Single protein structure of sequence from Sorangium cellulosum. 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

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