title: Homology modeling of nematode Caenorhabditis elegans CED3 protein-inhibitor complex.
abstract: CED3 protein, the product of a gene necessary for programmed cell death in the nematode Caenorhabditis elegans, is related to a highly specific cysteine protease family i.e., caspases. A tertiary-structural model has been constructed of a complex of the CED3 protein with tetrapeptide-aldehyde inhibitor, Ac-DEVD-CHO. The conformation of CED3 protein active site and the general binding features of inhibitor residues are similar to those observed in other caspases. The loop segment (Phe380-Pro387) binds with the P4 Asp in a different fashion compared to caspase-3. The comparative modeling of active sites from caspase-3 and CED3 protein indicated that although these enzymes require Asp at the position P4, variation could occur in the binding of this residue at the S4 subsite. This model allowed the definition of substrate specificity of CED3 protein from the structural standpoint and provided insight in designing of mutants for structure-function studies of this classical caspase homologue.
authors.affiliation: HEJ Research Institute of Chemistry, University of Karachi, Karachi, 75270, Pakistan.
authors.forename: M K
authors.initials: MK
authors.lastname: Azim
authors.forename: J G
authors.initials: JG
authors.lastname: Grossmann
authors.forename: Z H
authors.initials: ZH
authors.lastname: Zaidi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D001665:Binding Sites; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D053148:Caspase 3; D020169:Caspases / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D029742:Caenorhabditis elegans Proteins; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D001224:Aspartic Acid; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans