title: Ligand-binding prediction in the resistance-nodulation-cell division (RND) proteins.
abstract: The resistance-nodulation-cell division (RND) protein family is a ubiquitous group of proteins primarily present in bacteria. These proteins, involved in the transport of multiple drugs across the cell envelope in bacteria, exhibit broad substrate specificity and act like efflux pumps. In this work, a protein belonging to the RND protein family, AcrB of Escherichia coli was used as a working model to predict in silico the compounds transported by 47 RND proteins. From AcrB we extracted and clustered 14 amino acids directly involved in substrate interactions. This clustering provides enough information to identify 16 groups that correlates with the ligand they extrude, such as proteins expelling aromatic hydrocarbons (SrpB cluster) or proteins expelling heavy metals (CnrA cluster). The relationship between conserved, cluster-specific and variable residues indicates that although the ligand-binding domain is conserved in structure, it has enough flexibility to recognize specifically a diversity of molecules.
authors.affiliation: Departmento de Biología Molecular de Plantas, Instituto de Biotecnologia, Universidad Nacional Autónoma de México, A.P. 565-A Cuernavaca, Morelos 62210, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Hernandez-Mendoza
authors.forename: Carmen
authors.initials: C
authors.lastname: Quinto
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Segovia
authors.forename: Ernesto
authors.initials: E
authors.lastname: Perez-Rueda
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D008024:Ligands; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D008024:Ligands; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083496:AcrB protein, E coli