title: Protein recognition of adenylate: an example of a fuzzy recognition template.
abstract: The interaction between protein and adenylate in a non-homologous dataset of 18 high-resolution protein/nucleotide crystal structures is analysed. We find that each constituent of adenylate, adenine, ribose and phosphate, is substantially buried. Adenine has a largely hydrophobic protein interface, while phosphate interacts primarily with hydrophilic residues; ribose is intermediate. A detailed study of hydrogen bonding in these complexes shows hydrogen bonds between protein and adenine to be surprisingly scarce. There does not seem to be a conserved hydrogen-bonding pattern for adenine recognition. The hydrogen bonds that are seen have geometries close to energy minima found in our Distributed Multipole Analysis based model calculations. The experimental hydrogen-bonded geometries have a characteristic signature in our model energy calculations, with a dominant attractive electrostatic term. For stacked interactions, however, the dispersion energy dominates. Finally, we present the concept of a fuzzy recognition template, as a useful means of describing the protein/adenylate interactions presented here, which will also be a valuable concept for characterising other protein/ligand interactions.
authors.affiliation: Department of Biochemistry and Molecular Biology, University College, London, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Moodie
authors.forename: J B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: J M
authors.initials: JM
authors.lastname: Thornton
mesh_terms: D000225:Adenine / Q000737:chemistry; D000227:Adenine Nucleotides / Q000737:chemistry* / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D016208:Databases, Factual; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D010710:Phosphates / Q000737:chemistry; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012266:Ribose / Q000737:chemistry; D012984:Software; D013816:Thermodynamics
chemical_list: D000227:Adenine Nucleotides; D000596:Amino Acids; D008024:Ligands; D010710:Phosphates; D011506:Proteins; D012266:Ribose; D000225:Adenine