N??* Interactions Modulate the Properties of Cysteine Residues and Disulfide Bonds in Proteins.

ABSTRACT: Noncovalent interactions are ubiquitous in biology, taking on roles that include stabilizing the conformation of and assembling biomolecules, and providing an optimal environment for enzymatic catalysis. Here, we describe a noncovalent interaction that engages the sulfur atoms of cysteine residues and disulfide bonds in proteins-their donation of electron density into an antibonding orbital of proximal amide carbonyl groups. This n? ?* interaction tunes the reactivity of the CXXC motif, which is the critical feature of thioredoxin and other enzymes involved in redox homeostasis. In particular, an n? ?* interaction lowers the p Ka value of the N-terminal cysteine residue of the motif, which is the nucleophile that initiates catalysis. In addition, the interplay between disulfide n? ?* interactions and C5 hydrogen bonds leads to hyperstable ?-strands. Finally, n? ?* interactions stabilize vicinal disulfide bonds, which are naturally diverse in function. These previously unappreciated n? ?* interactions are strong and underlie the ability of cysteine residues and disulfide bonds to engage in the structure and function of proteins.

SUBMITTER: Kilgore HR 

PROVIDER: S-EPMC6527516 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature