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4etw

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Structure of the Enzyme-ACP Substrate Gatekeeper Complex Required for Biotin Synthesis

Structural highlights

4etw is a 4 chain structure with sequence from Shigella flexneri and Shigella flexneri 5 str. 8401. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACP_SHIF8 Carrier of the growing fatty acid chain in fatty acid biosynthesis.[HAMAP-Rule:MF_01217]

Publication Abstract from PubMed

Although the pimeloyl moiety was long known to be a biotin precursor, the mechanism of assembly of this C7 alpha,omega-dicarboxylic acid was only recently elucidated. In Escherichia coli, pimelate is made by bypassing the strict specificity of the fatty acid synthetic pathway. BioC methylates the free carboxyl of a malonyl thioester, which replaces the usual acetyl thioester primer. This atypical primer is transformed to pimeloyl-acyl carrier protein (ACP) methyl ester by two cycles of fatty acid synthesis. The question is, what stops this product from undergoing further elongation? Although BioH readily cleaves this product in vitro, the enzyme is nonspecific, which made assignment of its physiological substrate problematical, especially because another enzyme, BioF, could also perform this gatekeeping function. We report the 2.05-A resolution cocrystal structure of a complex of BioH with pimeloyl-ACP methyl ester and use the structure to demonstrate that BioH is the gatekeeper and its physiological substrate is pimeloyl-ACP methyl ester.

Structure of the enzyme-acyl carrier protein (ACP) substrate gatekeeper complex required for biotin synthesis.,Agarwal V, Lin S, Lukk T, Nair SK, Cronan JE Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17406-11. doi:, 10.1073/pnas.1207028109. Epub 2012 Oct 8. PMID:23045647^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Agarwal V, Lin S, Lukk T, Nair SK, Cronan JE. Structure of the enzyme-acyl carrier protein (ACP) substrate gatekeeper complex required for biotin synthesis. Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17406-11. doi:, 10.1073/pnas.1207028109. Epub 2012 Oct 8. PMID:23045647 doi:http://dx.doi.org/10.1073/pnas.1207028109