PDBsum entry: 3coj

Antitumor protein/ligase

PDB id: 3coj

Contents

Protein chains

(+ 2 more) 208 a.a. *

13 a.a. *

Ligands

PRO-GLN-SEP-PRO-THR-PHE-PRO-GLU-ALA-GLY ×4

PRO-GLN-SEP-PRO-THR-PHE-PRO ×2

GLN-SEP-PRO-THR-PHE

* Residue conservation analysis

PDB id:

3coj

Name:

Antitumor protein/ligase

Title:

Crystal structure of the brct domains of human brca1 in comp phosphorylated peptide from human acetyl-coa carboxylase 1

Structure:

Breast cancer type 1 susceptibility protein. Chain: x, a, b, c, d, e, f, g. Fragment: brct1 and brct2 domains. Synonym: ring finger protein 53. Engineered: yes. Acetyl-coa carboxylase 1. Chain: h, i, j, k, l, m, n, o. Fragment: residues 1258-1270. Synonym: acc-alpha.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: brca1, rnf53. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthesized human acc1 peptide with ser1263 phosphorylated.

Resolution:

3.21Å R-factor: 0.260 R-free: 0.307

Authors:

Y.Shen,L.Tong

Key ref:

Y.Shen and L.Tong (2008). Structural evidence for direct interactions between the BRCT domains of human BRCA1 and a phospho-peptide from human ACC1. Biochemistry, 47, 5767-5773. PubMed id: 18452305 DOI: 10.1021/bi800314m

Date:

28-Mar-08 Release date: 27-May-08

Protein chains

P38398  (BRCA1_HUMAN) -  Breast cancer type 1 susceptibility protein

Seq: 1863 a.a.

Struc: 208 a.a.

Protein chain

Q13085  (ACACA_HUMAN) -  Acetyl-CoA carboxylase 1

Seq: 2346 a.a.

Struc: 13 a.a.

Enzyme reactions

• Enzyme class 1: Chain K: E.C.6.3.4.14 - Biotin carboxylase.
• Reaction: ATP + biotin-[carboxyl-carrier-protein] + CO₂ = ADP + phosphate + carboxy-biotin-[carboxyl-carrier-protein]

ATP + biotin-[carboxyl-carrier-protein] + CO(2) (Bound ligand (Het Group name = GLY) matches with 40.00% similarity) = ADP + phosphate (Bound ligand (Het Group name = SEP) matches with 50.00% similarity) + carboxy-biotin-[carboxyl-carrier-protein]

• Enzyme class 2: Chain K: E.C.6.4.1.2 - Acetyl-CoA carboxylase.
• Reaction: ATP + acetyl-CoA + HCO₃^- = ADP + phosphate + malonyl-CoA

ATP + acetyl-CoA + HCO(3)(-) = ADP + phosphate (Bound ligand (Het Group name = SEP) matches with 50.00% similarity) + malonyl-CoA

• Cofactor: Biotin

Biotin (Bound ligand (Het Group name = PHE) matches with 58.82% similarity)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (2 terms)
• Biological process: DNA repair (1 term)
• Biochemical function: DNA binding (2 terms)

reference

DOI no: 10.1021/bi800314m

Biochemistry 47:5767-5773 (2008)

PubMed id: 18452305

Structural evidence for direct interactions between the BRCT domains of human BRCA1 and a phospho-peptide from human ACC1.

Y.Shen, L.Tong.

ABSTRACT

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.