1n6b: Difference between revisions

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[[Image:1n6b.gif|left|200px]]
{{Seed}}
[[Image:1n6b.png|left|200px]]


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{{STRUCTURE_1n6b|  PDB=1n6b  |  SCENE=  }}  
{{STRUCTURE_1n6b|  PDB=1n6b  |  SCENE=  }}  


'''Microsomal Cytochrome P450 2C5/3LVdH Complex with a dimethyl derivative of sulfaphenazole'''
===Microsomal Cytochrome P450 2C5/3LVdH Complex with a dimethyl derivative of sulfaphenazole===




==Overview==
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The structure of rabbit microsomal cytochrome P450 2C5/3LVdH complexed with a substrate, 4-methyl-N-methyl-N-(2-phenyl-2H-pyrazol-3-yl)benzenesulfonamide (DMZ), was determined by X-ray crystallography to 2.3 A resolution. Substrate docking studies and electron density maps indicate that DMZ binds to the enzyme in two antiparallel orientations of the long axis of the substrate. One orientation places the principal site of hydroxylation, the 4-methyl group, 4.4 A from the heme Fe, whereas the alternate conformation positions the second, infrequent site of hydroxylation at &gt;5.9 A from the heme Fe. Comparison of this structure to that obtained previously for the enzyme indicates that the protein closes around the substrate and prevents open access of water from bulk solvent to the heme Fe. This reflects a approximately 1.5 A movement of the F and G helices relative to helix I. The present structure provides a complete model for the protein from residues 27-488 and defines two new helices F' and G'. The G' helix is likely to contribute to interactions of the enzyme with membranes. The relatively large active site, as compared to the volume occupied by the substrate, and the flexibility of the enzyme are likely to underlie the capacity of drug-metabolizing enzymes to metabolize structurally diverse substrates of different sizes.
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{{ABSTRACT_PUBMED_12767218}}


==About this Structure==
==About this Structure==
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[[Category: Progesterone 21-hydroxylase]]
[[Category: Progesterone 21-hydroxylase]]
[[Category: Pyrene hydroxylase]]
[[Category: Pyrene hydroxylase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 02:09:00 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 06:33:52 2008''

Revision as of 03:33, 28 July 2008

File:1n6b.png

Template:STRUCTURE 1n6b

Microsomal Cytochrome P450 2C5/3LVdH Complex with a dimethyl derivative of sulfaphenazole

Template:ABSTRACT PUBMED 12767218

About this Structure

1N6B is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.

Reference

Structure of a substrate complex of mammalian cytochrome P450 2C5 at 2.3 A resolution: evidence for multiple substrate binding modes., Wester MR, Johnson EF, Marques-Soares C, Dansette PM, Mansuy D, Stout CD, Biochemistry. 2003 Jun 3;42(21):6370-9. PMID:12767218

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