Understanding the molecular mechanism of enzyme dynamics of ribonuclease a through protonation/deprotonation of HIS48

Chang G. Ji, John Zhang

Research output: Contribution to journalArticle

Abstract

Molecular dynamics simulation is carried out to investigate the enzyme dynamics of RNase A with the HIS48 in three different states (HIP48 (protonated), HID48 (deprotonated), and H48A mutant). Insights derived from the current theoretical study, combined with the available experimental observations, enabled us to provide a microscopic picture for the efficient enzyme dynamics. Specifically, in the "closed" state or HIP48, the N-terminal hinge loop is intact and the enzyme remains in a relatively stable conformation which is preferred for catalytic reaction. Deprotonation of HIS48 induces the denaturing of this hinge-loop into a 3 10-helix, causing it to break the original interaction network around the loop-1 and drive the partial unfolding of the N-terminal. The enhanced dynamic motion of the N-terminal helix facilitates the release of the catalytic product (the rate limiting step) and speeds up the overall catalytic process. The current study established that HIS49 acts as a modulator for the transformation of conformational states through the perturbing of hydrogen bond networks across loop-1, the N-terminal helix, and other residues nearby. Our study suggests that HIS48 may also serve to transport loop-1's kinetic energy to the reaction center.

Original languageEnglish (US)
Pages (from-to)17727-17737
Number of pages11
JournalJournal of the American Chemical Society
Volume133
Issue number44
DOIs
StatePublished - Nov 9 2011

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Deprotonation
Protonation
Ribonucleases
Enzymes
Hinges
Pancreatic Ribonuclease
Molecular Dynamics Simulation
Kinetic energy
Modulators
Conformations
Molecular dynamics
Hydrogen
Hydrogen bonds
Theoretical Models
Computer simulation

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Understanding the molecular mechanism of enzyme dynamics of ribonuclease a through protonation/deprotonation of HIS48. / Ji, Chang G.; Zhang, John.

In: Journal of the American Chemical Society, Vol. 133, No. 44, 09.11.2011, p. 17727-17737.

Research output: Contribution to journalArticle

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