2zby

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'''Crystal structure of vitamin D hydroxylase cytochrome P450 105A1 (R84A mutant)'''
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===Crystal structure of vitamin D hydroxylase cytochrome P450 105A1 (R84A mutant)===
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==Overview==
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Vitamin D 3 (VD 3), a prohormone in mammals, plays a crucial role in the maintenance of calcium and phosphorus concentrations in serum. Activation of VD 3 requires 25-hydroxylation in the liver and 1alpha-hydroxylation in the kidney by cytochrome P450 (CYP) enzymes. Bacterial CYP105A1 converts VD 3 into 1alpha,25-dihydroxyvitamin D 3 (1alpha,25(OH) 2D 3) in two independent reactions, despite its low sequence identity with mammalian enzymes (&lt;21% identity). The present study determined the crystal structures of a highly active mutant (R84A) of CYP105A1 from Streptomyces griseolus in complex and not in complex with 1alpha,25(OH) 2D 3. The compound 1alpha,25(OH) 2D 3 is positioned 11 A from the iron atom along the I helix within the pocket. A similar binding mode is observed in the structure of the human CYP2R1-VD 3 complex, indicating a common substrate-binding mechanism for 25-hydroxylation. A comparison with the structure of wild-type CYP105A1 suggests that the loss of two hydrogen bonds in the R84A mutant increases the adaptability of the B' and F helices, creating a transient binding site. Further mutational analysis of the active site reveals that 25- and 1alpha-hydroxylations share residues that participate in these reactions. These results provide the structural basis for understanding the mechanism of the two-step hydroxylation that activates VD 3.
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(as it appears on PubMed at http://www.pubmed.gov), where 18314962 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18314962}}
==About this Structure==
==About this Structure==
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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 Tue Jul 29 12:21:29 2008''

Revision as of 09:21, 29 July 2008

Image:2zby.png

Template:STRUCTURE 2zby

Crystal structure of vitamin D hydroxylase cytochrome P450 105A1 (R84A mutant)

Template:ABSTRACT PUBMED 18314962

About this Structure

2ZBY is a Single protein structure of sequence from Streptomyces griseolus. Full crystallographic information is available from OCA.

Reference

Crystal Structure of CYP105A1 (P450SU-1) in Complex with 1alpha,25-Dihydroxyvitamin D3(,)., Sugimoto H, Shinkyo R, Hayashi K, Yoneda S, Yamada M, Kamakura M, Ikushiro S, Shiro Y, Sakaki T, Biochemistry. 2008 Apr 1;47(13):4017-27. Epub 2008 Mar 4. PMID:18314962

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