2bdm

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{{STRUCTURE_2bdm| PDB=2bdm | SCENE= }}
{{STRUCTURE_2bdm| PDB=2bdm | SCENE= }}
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'''Structure of Cytochrome P450 2B4 with Bound Bifonazole'''
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===Structure of Cytochrome P450 2B4 with Bound Bifonazole===
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==Overview==
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To better understand ligand-induced structural transitions in cytochrome P450 2B4, protein-ligand interactions were investigated using a bulky inhibitor. Bifonazole, a broad spectrum antifungal agent, inhibits monooxygenase activity and induces a type II binding spectrum in 2B4dH(H226Y), a modified enzyme previously crystallized in the presence of 4-(4-chlorophenyl)imidazole (CPI). Isothermal titration calorimetry and tryptophan fluorescence quenching indicate no significant burial of protein apolar surface nor altered accessibility of Trp-121 upon bifonazole binding, in contrast to recent results with CPI. A 2.3 A crystal structure of 2B4-bifonazole reveals a novel open conformation with ligand bound in the active site, which is significantly different from either the U-shaped cleft of ligand-free 2B4 or the small active site pocket of 2B4-CPI. The O-shaped active site cleft of 2B4-bifonazole is widely open in the middle but narrow at the top. A bifonazole molecule occupies the bottom of the active site cleft, where helix I is bent approximately 15 degrees to accommodate the bulky ligand. The structure also defines unanticipated interactions between helix C residues and bifonazole, suggesting an important role of helix C in azole recognition by mammalian P450s. Comparison of the ligand-free 2B4 structure, the 2B4-CPI structure, and the 2B4-bifonazole structure identifies structurally plastic regions that undergo correlated conformational changes in response to ligand binding. The most plastic regions are putative membrane-binding motifs involved in substrate access or substrate binding. The results allow us to model the membrane-associated state of P450 and provide insight into how lipophilic substrates access the buried active site.
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{{ABSTRACT_PUBMED_16373351}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction., Zhao Y, White MA, Muralidhara BK, Sun L, Halpert JR, Stout CD, J Biol Chem. 2006 Mar 3;281(9):5973-81. Epub 2005 Dec 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16373351 16373351]
Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction., Zhao Y, White MA, Muralidhara BK, Sun L, Halpert JR, Stout CD, J Biol Chem. 2006 Mar 3;281(9):5973-81. Epub 2005 Dec 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16373351 16373351]
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An open conformation of mammalian cytochrome P450 2B4 at 1.6-A resolution., Scott EE, He YA, Wester MR, White MA, Chin CC, Halpert JR, Johnson EF, Stout CD, Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13196-201. Epub 2003 Oct 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14563924 14563924]
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Structure of mammalian cytochrome P450 2B4 complexed with 4-(4-chlorophenyl)imidazole at 1.9-A resolution: insight into the range of P450 conformations and the coordination of redox partner binding., Scott EE, White MA, He YA, Johnson EF, Stout CD, Halpert JR, J Biol Chem. 2004 Jun 25;279(26):27294-301. Epub 2004 Apr 20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15100217 15100217]
[[Category: Oryctolagus cuniculus]]
[[Category: Oryctolagus cuniculus]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
[[Category: P450]]
[[Category: P450]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:08:44 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:17:24 2008''

Revision as of 03:17, 29 July 2008

Image:2bdm.png

Template:STRUCTURE 2bdm

Structure of Cytochrome P450 2B4 with Bound Bifonazole

Template:ABSTRACT PUBMED 16373351

About this Structure

2BDM is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.

Reference

Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction., Zhao Y, White MA, Muralidhara BK, Sun L, Halpert JR, Stout CD, J Biol Chem. 2006 Mar 3;281(9):5973-81. Epub 2005 Dec 21. PMID:16373351

An open conformation of mammalian cytochrome P450 2B4 at 1.6-A resolution., Scott EE, He YA, Wester MR, White MA, Chin CC, Halpert JR, Johnson EF, Stout CD, Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13196-201. Epub 2003 Oct 16. PMID:14563924

Structure of mammalian cytochrome P450 2B4 complexed with 4-(4-chlorophenyl)imidazole at 1.9-A resolution: insight into the range of P450 conformations and the coordination of redox partner binding., Scott EE, White MA, He YA, Johnson EF, Stout CD, Halpert JR, J Biol Chem. 2004 Jun 25;279(26):27294-301. Epub 2004 Apr 20. PMID:15100217

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