title: Secbase: database module to retrieve secondary structure elements with ligand binding motifs.
abstract: Secbase is presented as a novel extension module of Relibase. It integrates the information about secondary structure elements into the retrieval facilities of Relibase. The data are accessible via the extended Relibase user interface, and integrated retrieval queries can be addressed using an extended version of Reliscript. The primary information about alpha-helices and beta-sheets is used as provided by the PDB. Furthermore, a uniform classification of all turn families, based on recent clustering methods, and a new helix assignment that is based on this turn classification has been included. Algorithms to analyze the geometric features of helices and beta-strands were also implemented. To demonstrate the performance of the Secbase implementation, some application examples are given. They provide new insights into the involvement of secondary structure elements in ligand binding. A survey of water molecules detected next to the N-terminus of helices is analyzed to show their involvement in ligand binding. Additionally, the parallel oriented NH groups at the alpha-helix N-termini provide special binding motifs to bind particular ligand functional groups with two adjacent oxygen atoms, e.g., as found in negatively charged carboxylate or phosphate groups, respectively. The present study also shows that the specific structure of the first turn of alpha-helices provides a suitable explanation for stabilizing charged structures. The magnitude of the overall helix macrodipole seems to have no or only a minor influence on binding. Furthermore, an overview of the involvement of secondary structure elements with the recognition of some important endogenous ligands such as cofactors shows some distinct preference for particular binding motifs and amino acids.
authors.affiliation: Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, D-35032 Marburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Koch
authors.forename: Jason
authors.initials: J
authors.lastname: Cole
authors.forename: Peter
authors.initials: P
authors.lastname: Block
authors.forename: Gerhard
authors.initials: G
authors.lastname: Klebe
mesh_terms: D000465:Algorithms; D000577:Amides / Q000378:metabolism; D020816:Amino Acid Motifs; D030562:Databases, Protein; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D014584:User-Computer Interface; D014867:Water / Q000378:metabolism
chemical_list: D000577:Amides; D008024:Ligands; D011506:Proteins; D014867:Water