title: Analysis of a three-dimensional structure of human acidic mammalian chitinase obtained by homology modeling and ligand binding studies.
abstract: The three-dimensional (3D) model of the human acidic mammalian chitinase (hAMCase) was constructed based on the crystal structure of the human chitotriosidase (EC 3.2.1.44, PDB code 1HKK) by using InsightII/Homology module. With the aid of molecular mechanics and molecular dynamics methods, the last refined model was obtained and further assessed by Profile-3D and Procheck, which confirms that the refined model is reliable. Furthermore, the docking results of the ligands (allosamidin and NAG(2)) into the active site of hAMCase indicate that allosamidin is a more preferred ligand than NAG(2), and that Glu119 forms hydrogen bond with allosamidin, which is in good agreement with the experimental results. From the docking studies, we also suggest that Trp10, Glu49, Asp192, and Glu276 in hAMCase are four important determinant residues in binding as they have strong van-der-Waals and electrostatic interactions with the ligand, respectively.
authors.affiliation: State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, P. R. China.
authors.forename: Yong-Shan
authors.initials: YS
authors.lastname: Zhao
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Zheng
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhang
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Chu
authors.forename: Chia-Chung
authors.initials: CC
authors.lastname: Sun
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D002686:Chitin / Q000737:chemistry; D002688:Chitinases / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D012984:Software; D055672:Static Electricity; D040681:Structural Homology, Protein; D013816:Thermodynamics; D014312:Trisaccharides / Q000737:chemistry
chemical_list: D008024:Ligands; D014312:Trisaccharides; C054851:allosamidin; D002686:Chitin; C499254:CHIA protein, human; D002688:Chitinases; D000117:Acetylglucosamine