Structure–Function Analysis of the Extended Conformation of a Polyketide Synthase Module
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. Furthermore, the extended conformation of a PKS module is fully competent for all of its essential catalytic functions.
- Authors:
-
- Stanford Univ., Stanford, CA (United States)
- University of California San Francisco, San Francisco, CA (United States)
- Stanford Univ., Stanford, CA (United States); SLAC National Accelerator Lab., Stanford Univ., Menlo Park, CA (United States)
- SLAC National Accelerator Lab., Stanford Univ., Menlo Park, CA (United States)
- Brown Univ., Providence, RI (United States)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1476142
- Grant/Contract Number:
- AC02-76SF00515; P41CA196276; GM022172; GM104659; GM087934
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of the American Chemical Society
- Additional Journal Information:
- Journal Volume: 140; Journal Issue: 21; Journal ID: ISSN 0002-7863
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
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. Structure–Function Analysis of the Extended Conformation of a Polyketide Synthase Module. United States: N. p., 2018.
Web. doi:10.1021/jacs.8b02100.
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., & Khosla, Chaitan. Structure–Function Analysis of the Extended Conformation of a Polyketide Synthase Module. United States. https://doi.org/10.1021/jacs.8b02100
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. Tue .
"Structure–Function Analysis of the Extended Conformation of a Polyketide Synthase Module". United States. https://doi.org/10.1021/jacs.8b02100. https://www.osti.gov/servlets/purl/1476142.
@article{osti_1476142,
title = {Structure–Function Analysis of the Extended Conformation of a Polyketide Synthase Module},
author = {Li, Xiuyuan and Sevillano, Natalia and La Greca, Florencia and Deis, Lindsay and Liu, Yu -Chen and Deller, Marc C. and Mathews, Irimpan I. and Matsui, Tsutomu and Cane, David E. and Craik, Charles S. and Khosla, Chaitan},
abstractNote = {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. Furthermore, the extended conformation of a PKS module is fully competent for all of its essential catalytic functions.},
doi = {10.1021/jacs.8b02100},
journal = {Journal of the American Chemical Society},
number = 21,
volume = 140,
place = {United States},
year = {Tue May 15 00:00:00 EDT 2018},
month = {Tue May 15 00:00:00 EDT 2018}
}
Web of Science
Figures / Tables:
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