Open AccessShining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation
Author(s) -
van den Bedem Henry,
Wilson Mark A
Publication year - 2019
Publication title -
journal of synchrotron radiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 99
ISSN - 1600-5775
DOI - 10.1107/s160057751900568x
Subject(s) - cysteine , sulfenic acid , covalent bond , chemistry , steric effects , conformational change , function (biology) , cysteine metabolism , protein structure , amino acid , structural biology , combinatorial chemistry , biophysics , biochemistry , stereochemistry , organic chemistry , enzyme , biology , evolutionary biology
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. 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.