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| | {{STRUCTURE_2q6n| PDB=2q6n | SCENE= }} | | {{STRUCTURE_2q6n| PDB=2q6n | SCENE= }} |
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| - | '''Structure of Cytochrome P450 2B4 with Bound 1-(4-cholorophenyl)imidazole'''
| + | ===Structure of Cytochrome P450 2B4 with Bound 1-(4-cholorophenyl)imidazole=== |
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| - | ==Overview==
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| - | The crystal structure of P450 2B4 bound with 1-(4-chlorophenyl)imidazole (1-CPI) has been determined to delineate the structural basis for the observed differences in binding affinity and thermodynamics relative to 4-(4-chlorophenyl)imidazole (4-CPI). Compared with the previously reported 4-CPI complex, there is a shift in the 1-CPI complex of the protein backbone in helices F and I, repositioning the side chains of Phe-206, Phe-297, and Glu-301, and leading to significant reshaping of the active site. Phe-206 and Phe-297 exchange positions, with Phe-206 becoming a ligand-contact residue, while Glu-301, rather than hydrogen bonding to the ligand, flips away from the active site and interacts with His-172. As a result the active site volume expands from 200 A3 in the 4-CPI complex to 280 A3 in the 1-CPI complex. Based on the two structures, it was predicted that a Phe-206-->Ala substitution would alter 1-CPI but not 4-CPI binding. Isothermal titration calorimetry experiments indicated that this substitution had no effect on the thermodynamic signature of 4-CPI binding to 2B4. In contrast, relative to wild-type 1-CPI binding to F206A showed significantly less favorable entropy but more favorable enthalpy. This result is consistent with loss of the aromatic side chain and possible ordering of water molecules, now able to interact with Glu-301 and exposed residues in the I-helix. Hence, thermodynamic measurements support the active site rearrangement observed in the crystal structure of the 1-CPI complex and illustrate the malleability of the active site with the fine-tuning of residue orientations and thermodynamic signatures. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17887776}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17887776 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17887776}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| | [[Category: P450]] | | [[Category: P450]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:26:57 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:06:27 2008'' |
Revision as of 15:06, 27 July 2008
Template:STRUCTURE 2q6n
Structure of Cytochrome P450 2B4 with Bound 1-(4-cholorophenyl)imidazole
Template:ABSTRACT PUBMED 17887776
About this Structure
2Q6N is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
Reference
Structural and thermodynamic consequences of 1-(4-chlorophenyl)imidazole binding to cytochrome P450 2B4., Zhao Y, Sun L, Muralidhara BK, Kumar S, White MA, Stout CD, Halpert JR, Biochemistry. 2007 Oct 16;46(41):11559-67. Epub 2007 Sep 22. PMID:17887776
Page seeded by OCA on Sun Jul 27 18:06:27 2008
