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| - | [[Image:2z3t.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2z3t| PDB=2z3t | SCENE= }} | | {{STRUCTURE_2z3t| PDB=2z3t | SCENE= }} |
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| - | '''Crystal Structure of Substrate Free Cytochrome P450 StaP (CYP245A1)'''
| + | ===Crystal Structure of Substrate Free 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17606921}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17606921 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17606921}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Monoxygenase]] | | [[Category: Monoxygenase]] |
| | [[Category: Oxydoreductase]] | | [[Category: Oxydoreductase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 19:55:39 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:17:44 2008'' |
Revision as of 00:17, 28 July 2008
Template:STRUCTURE 2z3t
Crystal Structure of Substrate Free Cytochrome P450 StaP (CYP245A1)
Template:ABSTRACT PUBMED 17606921
About this Structure
2Z3T 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
Page seeded by OCA on Mon Jul 28 03:17:44 2008
