Structure-Function Analysis of the Extended Conformation of a Polyketide Synthase Module

Journal of the American Chemical Society
Xiuyuan LiChaitan Khosla

Abstract

Catalytic modules of assembly-line polyketide synthases (PKSs) have previously been observed in two very different conformations-an "extended" architecture and an "arch-shaped" architecture-although the catalytic relevance of neither has been directly established. By the use of a fully human naïve antigen-binding fragment (Fab) library, a high-affinity antibody was identified that bound to the extended conformation of a PKS module, as verified by X-ray crystallography and tandem size-exclusion chromatography-small-angle X-ray scattering (SEC-SAXS). Kinetic analysis proved that this antibody-stabilized module conformation was fully competent for catalysis of intermodular polyketide chain translocation as well as intramodular polyketide chain elongation and functional group modification of a growing polyketide chain. Thus, the extended conformation of a PKS module is fully competent for all of its essential catalytic functions.

References

Mar 2, 2006·Journal of the American Chemical Society·Alice Y ChenChaitan Khosla
Jul 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yinyan TangChaitan Khosla
Jun 3, 2008·Journal of Molecular Biology·Christopher J FaradyCharles S Craik
Sep 6, 2008·Science·Timm MaierNenad Ban
Apr 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Serdar UysalAnthony Kossiakoff
Nov 22, 2011·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Thomas J MaliaGary L Gilliland
Oct 29, 2013·Journal of the American Chemical Society·Brian LowryChaitan Khosla
Apr 8, 2014·Journal of Molecular Biology·Andrea L EdwardsChaitan Khosla
Jun 27, 2014·Nature·Somnath DuttaGeorgios Skiniotis
Jun 9, 2016·Current Opinion in Structural Biology·Thomas RobbinsChaitan Khosla

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Citations

Sep 7, 2018·Natural Product Reports·Greg J DodgeJanet L Smith
Oct 4, 2018·Natural Product Reports·Simone KosolGregory L Challis
Mar 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuan ZhouLing Jiang
Aug 24, 2018·Natural Product Reports·Dominik A HerbstTimm Maier
Jan 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Naoki HorikoshiSoichi Wakatsuki
Mar 9, 2019·Current Opinion in Biotechnology·Koli BasuCharles S Craik
Aug 8, 2020·Current Opinion in Chemical Biology·Alexandra A MalicoGavin J Williams
Jun 19, 2021·Chemical Society Reviews·Dong YiUwe T Bornscheuer
Jan 27, 2019·ACS Chemical Biology·Maja KlausMartin Grininger
Aug 14, 2020·ACS Chemical Biology·Maja KlausMartin Grininger
Aug 14, 2020·Journal of the American Chemical Society·Dillon P CoganChaitan Khosla
Oct 1, 2021·ACS Chemical Biology·Melissa HirschAdrian T Keatinge-Clay

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