1w93

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{{STRUCTURE_1w93| PDB=1w93 | SCENE= }}
{{STRUCTURE_1w93| PDB=1w93 | SCENE= }}
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'''CRYSTAL STRUCTURE OF BIOTIN CARBOXYLASE DOMAIN OF ACETYL-COENZYME A CARBOXYLASE FROM SACCHAROMYCES CEREVISIAE'''
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===CRYSTAL STRUCTURE OF BIOTIN CARBOXYLASE DOMAIN OF ACETYL-COENZYME A CARBOXYLASE FROM SACCHAROMYCES CEREVISIAE===
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==Overview==
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Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism. Soraphen A, a macrocyclic polyketide natural product, is a nanomolar inhibitor against the biotin carboxylase (BC) domain of human, yeast, and other eukaryotic ACCs. Here we report the crystal structures of the yeast BC domain, alone and in complex with soraphen A. Soraphen has extensive interactions with an allosteric site, about 25 A from the active site. The specificity of soraphen is explained by large structural differences between the eukaryotic and prokaryotic BC in its binding site, confirmed by our studies on the effects of single-site mutations in this binding site. Unexpectedly, our structures suggest that soraphen may bind in the BC dimer interface and inhibit the BC activity by disrupting the oligomerization of this domain. Observations from native gel electrophoresis confirm this structural insight. The structural information provides a foundation for structure-based design of new inhibitors against these enzymes.
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{{ABSTRACT_PUBMED_15610732}}
==About this Structure==
==About this Structure==
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[[Category: Polyketide]]
[[Category: Polyketide]]
[[Category: Structure-based drug design]]
[[Category: Structure-based drug design]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:19:41 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:09:52 2008''

Revision as of 11:09, 28 July 2008

Image:1w93.png

Template:STRUCTURE 1w93

CRYSTAL STRUCTURE OF BIOTIN CARBOXYLASE DOMAIN OF ACETYL-COENZYME A CARBOXYLASE FROM SACCHAROMYCES CEREVISIAE

Template:ABSTRACT PUBMED 15610732

About this Structure

1W93 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

Reference

A mechanism for the potent inhibition of eukaryotic acetyl-coenzyme A carboxylase by soraphen A, a macrocyclic polyketide natural product., Shen Y, Volrath SL, Weatherly SC, Elich TD, Tong L, Mol Cell. 2004 Dec 22;16(6):881-91. PMID:15610732

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