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When fold is not important: A common structural framework for adenine and AMP binding in 12 unrelated protein families
Author(s) -
Denessiouk Konstantin A.,
Johnson Mark S.
Publication year - 2000
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(20000215)38:3<310::aid-prot7>3.0.co;2-t
Subject(s) - moiety , stereochemistry , ribonucleotide , chemistry , protein subunit , dna ligase , ribonucleotide reductase , biochemistry , protein data bank , molecular recognition , protein structure , nucleotide , enzyme , molecule , organic chemistry , gene
Abstract ATP is a ligand common to many proteins, yet it is unclear whether common recognition patterns do exist among the many different folds that bind ATP. Previously, it was shown that cAMP‐dependent protein kinase, D ‐Ala: D ‐Ala ligase and the α‐subunit of the α 2 β 2 ribonucleotide reductase do share extensive common structural elements for ATP recognition although their folds are different. Here, we have made a survey of structures that bind ATP and compared them with the key features seen in these three proteins. Our survey shows that 12 different fold types share a specific recognition pattern for the adenine moiety, and 8 of these folds have a common structural framework for recognition of the AMP moiety of the ligand. The common framework consists of a tripeptide segment plus three additional residues, which provides similar polar and hydrophobic interactions between the protein and mononucleotide. Consensus interactions are represented by four key hydrogen bonds present in each fold type. Two of these four hydrogen bonds, together with three aliphatic residues, form a specific recognition pattern for the adenine moiety in all 12 folds. These similarities point to a structural‐functional requirement shared by these different mononucleotide‐binding proteins that represent at this time 28% of the adenine mononucleotide complexes found in the Brookhaven Protein Data Bank. Proteins 2000;38:310–326. © 2000 Wiley‐Liss, Inc.