Interaction of substrate uridyl 3',5'-adenosine with ribonuclease A: a molecular dynamics study

Biophysical Journal
K SeshadriS Vishveshwara

Abstract

A wealth of information available from x-ray crystallographic structures of enzyme-ligand complexes makes it possible to study interactions at the molecular level. However, further investigation is needed when i) the binding of the natural substrate must be characterized, because ligands in the stable enzyme-ligand complexes are generally inhibitors or the analogs of substrate and transition state, and when ii) ligand binding is in part poorly characterized. We have investigated these aspects in the binding of substrate uridyl 3',5'-adenosine (UpA) to ribonuclease A (RNase A). Based on the systematically docked RNase A-UpA complex resulting from our previous study, we have undertaken a molecular dynamics simulation of the complex with solvent molecules. The molecular dynamics trajectories of this complex are analyzed to provide structural explanations for varied experimental observations on the ligand binding at the B2 subsite of ribonuclease A. The present study suggests that B2 subsite stabilization can be effected by different active site groups, depending on the substrate conformation. Thus when adenosine ribose pucker is O4'-endo, Gln69 and Glu111 form hydrogen-bonding contacts with adenine base, and when it is C2'-endo, A...Continue Reading

Citations

May 12, 2010·The Journal of Physical Chemistry. B·Elena FormosoDarrin M York
Sep 22, 2001·Journal of Biomolecular Structure & Dynamics·K VelurajaZ A Rafi
Jan 1, 1997·Annual Review of Physical Chemistry·C L Perrin, J B Nielson
Nov 28, 2000·Proteins·M S Madhusudhan, S Vishveshwara
Oct 28, 2019·Frontiers in Pharmacology·Guillem Prats-EjarqueEster Boix

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