1. Structure–Function Analysis of the Extended Conformation of a Polyketide Synthase Module
- Author
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Li, Xiuyuan, Sevillano, Natalia, La Greca, Florencia, Deis, Lindsay, Liu, Yu-Chen, Deller, Marc C, Mathews, Irimpan I, Matsui, Tsutomu, Cane, David E, Craik, Charles S, and Khosla, Chaitan
- Subjects
Biocatalysis ,Crystallography ,X-Ray ,Humans ,Kinetics ,Models ,Molecular ,Polyketide Synthases ,Protein Conformation ,Scattering ,Small Angle ,X-Ray Diffraction ,Chemical Sciences ,General Chemistry - 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.
- Published
- 2018