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Solution structure and dynamics of oxytetracycline polyketide synthase acyl carrier protein from streptomyces rimosus

Findlow, Stuart C., Winsor, Claire, Simpson, Thomas J., Crosby, John and Crump, Matthew P. (2003) Solution structure and dynamics of oxytetracycline polyketide synthase acyl carrier protein from streptomyces rimosus Biochemistry, 42, (28), pp. 8423-8433. (doi:10.1021/bi0342259).

Record type: Article

Abstract

Type II polyketide synthases (PKSs) utilize a dedicated and essential acyl carrier protein (ACP) in the biosynthesis of a specific polyketide product. As part of our ongoing studies into the mechanisms and control of polyketide biosynthesis, we report the second structure of a polyketide synthase ACP. In this work, multidimensional, heteronuclear NMR was employed to investigate the structure and dynamics of the ACP involved in the biosynthesis of the commonly prescribed polyketide antibiotic, oxytetracycline (otc). An ensemble of 28 structures of the 95 amino acid otc ACP (9916Da) was computed by simulated annealing with the inclusion of 1132 experimental restraints. Atomic RMSDs about the mean structure for all 28 models is 0.66 Angstrom for backbone atoms, 1.15 Angstrom for all heavy atoms (both values calculated for the folded part of the protein (residues 3-80)), and 0.41 Angstrom for backbone atoms within secondary structure. Otc ACP adopts the typical right-handed, four-helix fold of currently known ACPs but with the addition of a 13-residue flexible C-terminus. A comparison of the global folds of all structurally characterized ACPs is described, illustrating that PKS ACPs show clear differences as well as similarities to FAS ACPs. N-15 relaxation experiments for the protein backbone also reveal that the long loop between helices I and II is flexible and helix II, a proposed site of protein-protein interactions, shows conformational exchange. The helices of the ACP form a rigid scaffold for the protein, but these are interspersed with an unusual proportion of flexible linker regions.

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Published date: 25 June 2003
Keywords: NMr spectroscopy, fatty acid, in-vitro, backbone dynamics, exchange rates, gene cluster, biosynthesis, glycylcyclines, identification, transferases
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 24031
URI: http://eprints.soton.ac.uk/id/eprint/24031
ISSN: 0006-2960
PURE UUID: 0c1d98ef-f897-40ab-ba58-a8b054ac83d6

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Date deposited: 17 Mar 2006
Last modified: 17 Jul 2017 16:15

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Contributors

Author: Stuart C. Findlow
Author: Claire Winsor
Author: Thomas J. Simpson
Author: John Crosby
Author: Matthew P. Crump

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