3coj

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'''Crystal Structure of the BRCT Domains of Human BRCA1 in Complex with a Phosphorylated Peptide from Human Acetyl-CoA Carboxylase 1'''
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===Crystal Structure of the BRCT Domains of Human BRCA1 in Complex with a Phosphorylated Peptide from Human Acetyl-CoA Carboxylase 1===
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==Overview==
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The tandem BRCA1 C-terminal (BRCT) domains are phospho-serine/threonine recognition modules essential for the function of BRCA1. Recent studies suggest that acetyl-CoA carboxylase 1 (ACC1), an enzyme with crucial roles in de novo fatty acid biosynthesis and lipogenesis and essential for cancer cell survival, may be a novel binding partner for BRCA1, through interactions with its BRCT domains. We report here the crystal structure at 3.2 A resolution of human BRCA1 BRCT domains in complex with a phospho-peptide from human ACC1 (p-ACC1 peptide, with the sequence 1258-DSPPQ-pS-PTFPEAGH-1271), which provides molecular evidence for direct interactions between BRCA1 and ACC1. The p-ACC1 peptide is bound in an extended conformation, located in a groove between the tandem BRCT domains. There are recognizable and significant structural differences to the binding modes of two other phospho-peptides to these domains, from BACH1 and CtIP, even though they share a conserved pSer-Pro-(Thr/Val)-Phe motif. Our studies establish a framework for understanding the regulation of lipid biosynthesis by BRCA1 through its inhibition of ACC1 activity, which could be a novel tumor suppressor function of BRCA1.
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{{ABSTRACT_PUBMED_18452305}}
==About this Structure==
==About this Structure==
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[[Category: Zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 28 09:22:35 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 12:13:16 2008''

Revision as of 09:13, 28 July 2008

Image:3coj.png

Template:STRUCTURE 3coj

Crystal Structure of the BRCT Domains of Human BRCA1 in Complex with a Phosphorylated Peptide from Human Acetyl-CoA Carboxylase 1

Template:ABSTRACT PUBMED 18452305

About this Structure

3COJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural evidence for direct interactions between the BRCT domains of human BRCA1 and a phospho-peptide from human ACC1., Shen Y, Tong L, Biochemistry. 2008 May 27;47(21):5767-73. Epub 2008 May 2. PMID:18452305

Page seeded by OCA on Mon Jul 28 12:13:16 2008

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