Dynamics of the native and the ligand-bound structures of eosinophil cationic protein: network of hydrogen bonds at the catalytic site.
Eosinophil Cationic Protein (ECP) is sequentially and structurally similar to ribonuclease A (RNase A). It belongs to the RNase A family of proteins and the RNA catalysis is essential to its biological function. In the present study, we have generated the dinucleotide-bound structures of ECP by docking the dinucleotides to a number of molecular dynamics (MD) generated ECP structures. The stability of the docked enzyme-ligand complexes was ascertained by extensive MD simulations. The modes of ligand binding are explored by essential dynamics studies. The role of water molecules in the stability of the complex and in the catalysis was investigated. The active site residues form a complex network of connections with the ligand and with a water molecule. The catalytic mechanism of the RNA cleavage is examined on the basis of the active site geometry obtained by the simulations.
Sanjeev
B S
BS
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
Vishveshwara
S
S
D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D047150:Eosinophil Cationic Protein / Q000138:chemical synthesis / Q000737:chemistry*; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011522:Protons; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D008024:Ligands; D009711:Nucleotides; D011522:Protons; D014867:Water; D047150:Eosinophil Cationic Protein; D012259:Ribonuclease, Pancreatic