Analysis of a three-dimensional structure of human acidic mammalian chitinase obtained by homology modeling and ligand binding studies

J Mol Model. 2009 May;15(5):499-505. doi: 10.1007/s00894-008-0430-9. Epub 2008 Dec 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / analogs & derivatives
  • Acetylglucosamine / chemistry
  • Amino Acid Sequence
  • Binding Sites
  • Chitin / chemistry
  • Chitinases / chemistry*
  • Humans
  • Hydrogen Bonding
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Sequence Alignment
  • Software
  • Static Electricity
  • Structural Homology, Protein*
  • Thermodynamics
  • Trisaccharides / chemistry

Substances

  • Ligands
  • Trisaccharides
  • allosamidin
  • Chitin
  • CHIA protein, human
  • Chitinases
  • Acetylglucosamine