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Analysis of Streptomyces coelicolor phosphopantetheinyl transferase, AcpS, reveals the basis for relaxed substrate specificity

DOI: 10.1021/bi2003668 DOI Help
PMID: 21595442 PMID Help

Authors: Patrick Dall'Aglio (University of Bristol) , Christopher J. Arthur (University of Bristol) , Christopher Williams (University of Bristol) , Konstantinos Vasilakis (University of Bristol) , Hannah J. Maple (University of Bristol) , John Crosby (University of Bristol) , Matthew P. Crump (University of Bristol) , Andrea Hadfield (University of Bristol)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochemistry , VOL 50 (25) , PAGES 5704 - 5717

State: Published (Approved)
Published: May 2011

Abstract: The transfer of the phosphopantetheine chain from coenzyme A (CoA) to the acyl carrier protein (ACP), a key protein in both fatty acid and polyketide synthesis, is catalyzed by ACP synthase (AcpS). Streptomyces coelicolor AcpS is a doubly promiscuous enzyme capable of activation of ACPs from both fatty acid and polyketide synthesis and catalyzes the transfer of modified CoA substrates. Five crystal structures have been determined, including those of ligand-free AcpS, complexes with CoA and acetyl-CoA, and two of the active site mutants, His110Ala and Asp111Ala. All five structures are trimeric and provide further insight into the mechanism of catalysis, revealing the first detailed structure of a group I active site with the essential magnesium in place. Modeling of ACP binding supported by mutational analysis suggests an explanation for the promiscuity in terms of both ACP partner and modified CoA substrates.

Journal Keywords: Bacterial; Catalytic; Crystallography; X-Ray; Escherichia; Ligands; Magnesium; Models; Molecular; Protein; Streptomyces; Substrate; Transferases; Transferases (Other Substituted Phosphate Groups)

Diamond Keywords: Bacteria; Enzymes

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I02-Macromolecular Crystallography

Other Facilities: 10.1 at SRS Daresbury

Added On: 28/11/2011 09:41

Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)