New insights for dinucleotide backbone binding in conserved C5′H…O hydrogen bonds

Abstract

Most enzymes that utilize dinucleotide NAD or NADP are known to comprise a glycine-rich loop segment (e.g. the GXGXXG signature motif of Rossman fold) which binds the cofactor’s diphosphate moiety. Through analysis of a set of diverse NAD(P)-bound protein structures, we show here that with few exceptions this diphosphate binding is complemented by a second loop segment interacting from a different angle with unconventional yet apparently ubiquitous CH…O hydrogen bonds formed between C5′ methylene of dinucleotide and, primarily, carbonyl oxygen of protein. This finding implicates an important role of C5′ in protein-nucleotide recognition.