Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation
Abstract
We report that cysteine is a rare but functionally important amino acid that is often subject to covalent modification. Cysteine oxidation plays an important role in many human disease processes, and basal levels of cysteine oxidation are required for proper cellular function. Because reactive cysteine residues are typically ionized to the thiolate anion (Cys-S-), their formation of a covalent bond alters the electrostatic and steric environment of the active site. X-ray-induced photo-oxidation to sulfenic acids (Cys-SOH) can recapitulate some aspects of the changes that occur under physiological conditions. Here we propose how site-specific cysteine photo-oxidation can be used to interrogate ensuing changes in protein structure and dynamics at atomic resolution. Although this powerful approach can connect cysteine covalent modification to global protein conformational changes and function, careful biochemical validation must accompany all such studies to exclude misleading artifacts. Lastly, new types of X-ray crystallography experiments and powerful computational methods are creating new opportunities to connect conformational dynamics to catalysis for the large class of systems that use covalently modified cysteine residues for catalysis or regulation.
- Authors:
-
[1];
- SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., CA (United States); Univ. of California, San Francisco, CA (United States)
- Univ. of Nebraska, Lincoln, NE (United States)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1546912
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Synchrotron Radiation (Online)
- Additional Journal Information:
- Journal Name: Journal of Synchrotron Radiation (Online); Journal Volume: 26; Journal Issue: 4; Journal ID: ISSN 1600-5775
- Publisher:
- International Union of Crystallography
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; cysteine modification; radiation-controlled photo-oxidation; serial X-ray crystallography; enzyme conformational dynamics; molecular dynamics simulations
Citation Formats
van den Bedem, Henry, and Wilson, Mark A. Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation. United States: N. p., 2019.
Web. https://doi.org/10.1107/s160057751900568x.
van den Bedem, Henry, & Wilson, Mark A. Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation. United States. https://doi.org/10.1107/s160057751900568x
van den Bedem, Henry, and Wilson, Mark A. Thu .
"Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation". United States. https://doi.org/10.1107/s160057751900568x. https://www.osti.gov/servlets/purl/1546912.
@article{osti_1546912,
title = {Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation},
author = {van den Bedem, Henry and Wilson, Mark A.},
abstractNote = {We report that cysteine is a rare but functionally important amino acid that is often subject to covalent modification. Cysteine oxidation plays an important role in many human disease processes, and basal levels of cysteine oxidation are required for proper cellular function. Because reactive cysteine residues are typically ionized to the thiolate anion (Cys-S-), their formation of a covalent bond alters the electrostatic and steric environment of the active site. X-ray-induced photo-oxidation to sulfenic acids (Cys-SOH) can recapitulate some aspects of the changes that occur under physiological conditions. Here we propose how site-specific cysteine photo-oxidation can be used to interrogate ensuing changes in protein structure and dynamics at atomic resolution. Although this powerful approach can connect cysteine covalent modification to global protein conformational changes and function, careful biochemical validation must accompany all such studies to exclude misleading artifacts. Lastly, new types of X-ray crystallography experiments and powerful computational methods are creating new opportunities to connect conformational dynamics to catalysis for the large class of systems that use covalently modified cysteine residues for catalysis or regulation.},
doi = {10.1107/s160057751900568x},
journal = {Journal of Synchrotron Radiation (Online)},
number = 4,
volume = 26,
place = {United States},
year = {2019},
month = {6}
}
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