Hydrogen bond stereochemistry in protein structure and function.

Fifty high resolution protein structures from the Brookhaven Protein Data Bank have been analyzed for recurring motifs in hydrogen bond stereochemistry. Although an exhaustive analysis of hydrogen bond statistics has been presented by Baker & Hubbard, a detailed stereochemical analysis of classical donor (N-H, O-H, or S-H) and acceptor (N:, O:, or S:) structure within proteins is lacking. Here, we describe the preferential hydrogen bond stereochemistry for the side-chains of glutamate and aspartate (carboxylate), glutamine and asparagine (carboxamide), arginine (guanidinium), histidine (imidazole/imidazolium), tryptophan (indole), tyrosine (phenolic hydroxyl), lysine (ammonium), serine and threonine (alkyl hydroxyl), cysteine (thiol), methionine (thioether) and cystine (disulfide). Preferential hydrogen bond stereochemistry is governed by (1) the electronic configuration of acceptor atoms, (2) the steric accessibility of donor atoms and (3) the conformation of amino acid side-chains. Applications of hydrogen bond stereochemistry are useful in the interpretation of protein structure, function and stability. Additionally, this stereochemistry is a prerequisite to the interpretation of protein-other molecule recognition and biological catalysis.