Acyl carrier protein (ACP)



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Minimized Average ACP structure
The side-chain for Ser-36, which attaches 4'-PP, is shown.
PDBID: 1HY8 Structure (2001), 9(4) 277-287.
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Acyl carrier protein (ACP) is a fundamental component of fatty acid biosynthesis where the fatty acid chain is elongated by the fatty acid synthetase system while attached to the 4’phosphopantetheine prosthetic group (4’-PP) of ACP. Activation of ACP is mediated by holo-acyl carrier protein synthase (ACPS) where ACPS transfers the 4’-PP moiety from coenzyme A (CoA) to Ser-36 of apo-ACP.  Both ACP and ACPS have been identified as essential for E. coli viability and potential targets for development of antibiotics.

Structural data was collected for both the apo- and holo-forms of ACP that suggest that the two forms of ACP are essentially identical. Comparison of the published structures for E. coli ACP and Actinorhodin Polyketide Synthase acyl carrier protein (act apo-ACP) from Streptomyces coelicolor A3(2)  with B. subtilis ACP indicates similar secondary structure elements, but an extremely large rms deviation between the three ACP structures (>4.3 Å).   The structural difference between B. subtilis ACP and both E. coli and act apo-ACP is not attributed to an inherent difference in the proteins but is probably a result of a limitation in the methodology available for the analysis for E. coli and act apo-ACP.  Comparison of the structure of free ACP with the bound form of ACP in the ACP-ACPS complex reveals a displacement of helix II in the vicinity of Ser-36.  The induced perturbation of ACP by ACPS positions Ser-36 proximal to coenzyme A and aligns the dipole of helix II to initiate transfer of 4’-PP to ACP.

 

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