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2z3u

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{{STRUCTURE_2z3u| PDB=2z3u | SCENE= }}
{{STRUCTURE_2z3u| PDB=2z3u | SCENE= }}
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'''Crystal Structure of Chromopyrrolic Acid Bound Cytochrome P450 StaP (CYP245A1)'''
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===Crystal Structure of Chromopyrrolic Acid Bound Cytochrome P450 StaP (CYP245A1)===
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==Overview==
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Staurosporine isolated from Streptomyces sp. TP-A0274 is a member of the family of indolocarbazole alkaloids that exhibit strong antitumor activity. A key step in staurosporine biosynthesis is the formation of the indolocarbazole core by intramolecular C-C bond formation and oxidative decarboxylation of chromopyrrolic acid (CPA) catalyzed by cytochrome P450 StaP (StaP, CYP245A1). In this study, we report x-ray crystal structures of CPA-bound and -free forms of StaP. Upon substrate binding, StaP adopts a more ordered conformation, and conformational rearrangements of residues in the active site are also observed. Hydrogen-bonding interactions of two carboxyl groups and T-shaped pi-pi interactions with indole rings hold the substrate in the substrate-binding cavity with a conformation perpendicular to the heme plane. Based on the crystal structure of StaP-CPA complex, we propose that C-C bond formation occurs through an indole cation radical intermediate that is equivalent to cytochrome c peroxidase compound I [Sivaraja M, Goodin DB, Smith M, Hoffman BM (1989) Science 245:738-740]. The subsequent oxidative decarboxylation reaction is also discussed based on the crystal structure. Our crystallographic study shows the first crystal structures of enzymes involved in formation of the indolocarbazole core and provides valuable insights into the process of staurosporine biosynthesis, combinatorial biosynthesis of indolocarbazoles, and the diversity of cytochrome P450 chemistry.
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==About this Structure==
==About this Structure==
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[[Category: Monoxygenase]]
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[[Category: Oxydoreductase]]
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Revision as of 19:42, 28 July 2008

Image:2z3u.png

Template:STRUCTURE 2z3u

Crystal Structure of Chromopyrrolic Acid Bound Cytochrome P450 StaP (CYP245A1)

Template:ABSTRACT PUBMED 17606921

About this Structure

2Z3U is a Single protein structure of sequence from Bacteria. Full crystallographic information is available from OCA.

Reference

Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces the indolocarbazole skeleton., Makino M, Sugimoto H, Shiro Y, Asamizu S, Onaka H, Nagano S, Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11591-6. Epub 2007 Jul 2. PMID:17606921

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