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Title: The Conformational Flexibility of the Acyltransferase from the Disorazole Polyketide Synthase Is Revealed by an X-ray Free-Electron Laser Using a Room-Temperature Sample Delivery Method for Serial Crystallography

The crystal structure of the trans-acyltransferase (AT) from the disorazole polyketide synthase (PKS) was determined at room temperature to a resolution of 2.5 Å using a new method for sample delivery directly into an X-ray free-electron laser. A novel sample extractor efficiently delivered limited quantities of microcrystals directly from the native crystallization solution into the X-ray beam at room temperature. The AT structure revealed important catalytic features of this core PKS enzyme, including the occurrence of conformational changes around the active site. The implications of these conformational changes on polyketide synthase reaction dynamics are discussed.
Authors:
ORCiD logo [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [5] ; ORCiD logo [2] ;  [1] ;  [1] ;  [1] ;  [6] ;  [6]
  1. SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
  2. Stanford Univ., CA (United States). Dept. of Chemistry
  3. SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL); Stanford Univ., CA (United States). Dept. of Molecular and Cellular Physiology
  4. Stanford Univ., CA (United States). Dept. of Molecular and Cellular Physiology
  5. Stanford Univ., CA (United States). Dept. of Molecular and Cellular Physiology; Howard Hughes Medical Inst., Chevy Chase, MD (United States)
  6. Stanford Synchrotron Radiation Lightsource, 2575 Sand Hill Road, Menlo Park, California 94025, United States
Publication Date:
Grant/Contract Number:
AC02-76SF00515; R01 GM087934
Type:
Accepted Manuscript
Journal Name:
Biochemistry
Additional Journal Information:
Journal Volume: 56; Journal Issue: 36; Journal ID: ISSN 0006-2960
Publisher:
American Chemical Society (ACS)
Research Org:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE
OSTI Identifier:
1393642

Mathews, Irimpan I., Allison, Kim, Robbins, Thomas, Lyubimov, Artem Y., Uervirojnangkoorn, Monarin, Brunger, Axel T., Khosla, Chaitan, DeMirci, Hasan, McPhillips, Scott E., Hollenbeck, Michael, Soltis, Michael, and Cohen, Aina E.. The Conformational Flexibility of the Acyltransferase from the Disorazole Polyketide Synthase Is Revealed by an X-ray Free-Electron Laser Using a Room-Temperature Sample Delivery Method for Serial Crystallography. United States: N. p., Web. doi:10.1021/acs.biochem.7b00711.
Mathews, Irimpan I., Allison, Kim, Robbins, Thomas, Lyubimov, Artem Y., Uervirojnangkoorn, Monarin, Brunger, Axel T., Khosla, Chaitan, DeMirci, Hasan, McPhillips, Scott E., Hollenbeck, Michael, Soltis, Michael, & Cohen, Aina E.. The Conformational Flexibility of the Acyltransferase from the Disorazole Polyketide Synthase Is Revealed by an X-ray Free-Electron Laser Using a Room-Temperature Sample Delivery Method for Serial Crystallography. United States. doi:10.1021/acs.biochem.7b00711.
Mathews, Irimpan I., Allison, Kim, Robbins, Thomas, Lyubimov, Artem Y., Uervirojnangkoorn, Monarin, Brunger, Axel T., Khosla, Chaitan, DeMirci, Hasan, McPhillips, Scott E., Hollenbeck, Michael, Soltis, Michael, and Cohen, Aina E.. 2017. "The Conformational Flexibility of the Acyltransferase from the Disorazole Polyketide Synthase Is Revealed by an X-ray Free-Electron Laser Using a Room-Temperature Sample Delivery Method for Serial Crystallography". United States. doi:10.1021/acs.biochem.7b00711. https://www.osti.gov/servlets/purl/1393642.
@article{osti_1393642,
title = {The Conformational Flexibility of the Acyltransferase from the Disorazole Polyketide Synthase Is Revealed by an X-ray Free-Electron Laser Using a Room-Temperature Sample Delivery Method for Serial Crystallography},
author = {Mathews, Irimpan I. and Allison, Kim and Robbins, Thomas and Lyubimov, Artem Y. and Uervirojnangkoorn, Monarin and Brunger, Axel T. and Khosla, Chaitan and DeMirci, Hasan and McPhillips, Scott E. and Hollenbeck, Michael and Soltis, Michael and Cohen, Aina E.},
abstractNote = {The crystal structure of the trans-acyltransferase (AT) from the disorazole polyketide synthase (PKS) was determined at room temperature to a resolution of 2.5 Å using a new method for sample delivery directly into an X-ray free-electron laser. A novel sample extractor efficiently delivered limited quantities of microcrystals directly from the native crystallization solution into the X-ray beam at room temperature. The AT structure revealed important catalytic features of this core PKS enzyme, including the occurrence of conformational changes around the active site. The implications of these conformational changes on polyketide synthase reaction dynamics are discussed.},
doi = {10.1021/acs.biochem.7b00711},
journal = {Biochemistry},
number = 36,
volume = 56,
place = {United States},
year = {2017},
month = {8}
}