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

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.

doi:10.1021/acs.biochem.7b00711

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

Journal Article · Wed Aug 23 00:00:00 EDT 2017 · Biochemistry

DOI:https://doi.org/10.1021/acs.biochem.7b00711· OSTI ID:1393642

^[1]; Allison, Kim ^[1]; Robbins, Thomas ^[2]; Lyubimov, Artem Y. ^[3]; Uervirojnangkoorn, Monarin ^[4]; Brunger, Axel T. ^[5];

^[2]; DeMirci, Hasan ^[1]; McPhillips, Scott E. ^[1]; Hollenbeck, Michael ^[1]; Soltis, Michael ^[6]; Cohen, Aina E. ^[6]

SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Stanford Univ., CA (United States). Dept. of Chemistry
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
Stanford Univ., CA (United States). Dept. of Molecular and Cellular Physiology
Stanford Univ., CA (United States). Dept. of Molecular and Cellular Physiology; Howard Hughes Medical Inst., Chevy Chase, MD (United States)
Stanford Synchrotron Radiation Lightsource, 2575 Sand Hill Road, Menlo Park, California 94025, United States

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.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)

Grant/Contract Number:: AC02-76SF00515; R01 GM087934

OSTI ID:: 1393642

Journal Information:: Biochemistry, Vol. 56, Issue 36; ISSN 0006-2960

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 16 works

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References (20)

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Protein–protein interactions in trans -AT polyketide synthases Kosol, Simone; Jenner, Matthew; Lewandowski, Józef R. Natural Product Reports, Vol. 35, Issue 10 https://doi.org/10.1039/c8np00066b	journal	January 2018
Strategies for sample delivery for femtosecond crystallography Martiel, Isabelle; Müller-Werkmeister, Henrike M.; Cohen, Aina E. Acta Crystallographica Section D Structural Biology, Vol. 75, Issue 2 https://doi.org/10.1107/s2059798318017953	journal	February 2019
A guide to sample delivery systems for serial crystallography Zhao, Feng‐Zhu; Zhang, Bin; Yan, Er‐Kai The FEBS Journal, Vol. 286, Issue 22 https://doi.org/10.1111/febs.15099	journal	August 2019
An outlook on using serial femtosecond crystallography in drug discovery Mishin, Alexey; Gusach, Anastasiia; Luginina, Aleksandra Expert Opinion on Drug Discovery, Vol. 14, Issue 9 https://doi.org/10.1080/17460441.2019.1626822	journal	May 2019
3D printed droplet generation devices for serial femtosecond crystallography enabled by surface coating Echelmeier, Austin; Kim, Daihyun; Cruz Villarreal, Jorvani Journal of Applied Crystallography, Vol. 52, Issue 5 https://doi.org/10.1107/s1600576719010343	journal	August 2019
Microfocus diffraction from different regions of a protein crystal: structural variations and unit-cell polymorphism Thompson, Michael C.; Cascio, Duilio; Yeates, Todd O. Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 5 https://doi.org/10.1107/s2059798318003479	journal	April 2018
Nylon mesh-based sample holder for fixed-target serial femtosecond crystallography Lee, Donghyeon; Baek, Sangwon; Park, Jaehyun Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-43485-z	journal	May 2019
Polysaccharide-Based Injection Matrix for Serial Crystallography Nam, Ki Hyun International Journal of Molecular Sciences, Vol. 21, Issue 9 https://doi.org/10.3390/ijms21093332	journal	May 2020
Strategies for sample delivery for femtosecond crystallography Martiel, Isabelle; Müller-Werkmeister, Henrike M.; Cohen, Aina E. International Union of Crystallography (IUCr) https://doi.org/10.1107/s2059798318017953/ba5296sup1.pdf	text	January 2019
Acyltransferases as Tools for Polyketide Synthase Engineering Musiol-Kroll, Ewa; Wohlleben, Wolfgang Antibiotics, Vol. 7, Issue 3 https://doi.org/10.3390/antibiotics7030062	journal	July 2018

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