2z3t

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[[Image:2z3t.gif|left|200px]]<br /><applet load="2z3t" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2z3t.gif|left|200px]]
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caption="2z3t, resolution 1.90&Aring;" />
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'''Crystal Structure of Substrate Free Cytochrome P450 StaP (CYP245A1)'''<br />
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{{Structure
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|PDB= 2z3t |SIZE=350|CAPTION= <scene name='initialview01'>2z3t</scene>, resolution 1.90&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene> and <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>
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|ACTIVITY=
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|GENE= staP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=114696 Streptomyces cangkringensis])
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}}
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'''Crystal Structure of Substrate Free Cytochrome P450 StaP (CYP245A1)'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2Z3T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_cangkringensis Streptomyces cangkringensis] with <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=IMD:'>IMD</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z3T OCA].
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2Z3T is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_cangkringensis Streptomyces cangkringensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z3T OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17606921 17606921]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/17606921 17606921]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Streptomyces cangkringensis]]
[[Category: Streptomyces cangkringensis]]
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[[Category: oxydoreductase]]
[[Category: oxydoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:59:58 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:51:51 2008''

Revision as of 16:51, 20 March 2008

Image:2z3t.gif


PDB ID 2z3t

Drag the structure with the mouse to rotate
, resolution 1.90Å
Ligands: , and
Gene: staP (Streptomyces cangkringensis)
Coordinates: save as pdb, mmCIF, xml



Crystal Structure of Substrate Free Cytochrome P450 StaP (CYP245A1)


Overview

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.

About this Structure

2Z3T is a Single protein structure of sequence from Streptomyces cangkringensis. 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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