New insights for dinucleotide backbone binding in conserved C5′-H•••O hydrogen bonds

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. (C) 1998 Academic Press Limited.