title: A consensus-binding structure for adenine at the atomic level permits searching for the ligand site in a wide spectrum of adenine-containing complexes.
abstract: Attempts to derive structural features of ligand-binding sites have traditionally involved seeking commonalities at the residue level. Recently, structural studies have turned to atomic interactions of small molecular fragments to extract common binding-site properties. Here, we explore the use of larger ligand elements to derive a consensus binding structure for the ligand as a whole. We superimposed multiple molecular structures from a nonredundant set of adenosine-5'-triphosphate (ATP) protein complexes, using the adenine moiety as template. Clustered binding-site atoms of compatible atomic classes forming attractive contacts with the adenine probe were extracted. A set of atomic clusters characterizing the adenine binding pocket was then derived. Among the clusters are three vertices representing the interactions of adenine atom N6 with its protein-binding niche. These vertices, together with atom C6 of the purine ring system, complete the set of four vertices for the pyramid-like structure of the N6 anchor atom. Also, the sequence relationship for the adenine-binding loop interacting with the C2-N6 end of the conjugated ring system is expanded to include a third hydrophilic cluster interacting with atom N1. A search procedure involving interatomic distances between cluster centers was formulated and applied to seek putative binding sites in test cases. The results show that a consensus network of clusters, based on an adenine probe and an ATP-complexed training set of proteins, is sufficient to recognize the experimental cavity for adenine in a wide spectrum of ligand-protein complexes.
authors.affiliation: Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yosef Y
authors.initials: YY
authors.lastname: Kuttner
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sobolev
authors.forename: Alexander
authors.initials: A
authors.lastname: Raskind
authors.forename: Marvin
authors.initials: M
authors.lastname: Edelman
mesh_terms: D000225:Adenine / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012984:Software
chemical_list: D008024:Ligands; D011506:Proteins; D000255:Adenosine Triphosphate; D000225:Adenine