Next Article in Journal
Transcriptomic Analysis of Phenotypic Changes in Birch (Betula platyphylla) Autotetraploids
Next Article in Special Issue
Preparation of Coaxial-Electrospun Poly[bis(p-methylphenoxy)]phosphazene Nanofiber Membrane for Enzyme Immobilization
Previous Article in Journal
Molecular Pathogenesis of Neuromyelitis Optica
Previous Article in Special Issue
Computational Protein Engineering: Bridging the Gap between Rational Design and Laboratory Evolution
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2012, 13(10), 12994-13011; doi:10.3390/ijms131012994

A Molecular Dynamics (MD) and Quantum Mechanics/Molecular Mechanics (QM/MM) Study on Ornithine Cyclodeaminase (OCD): A Tale of Two Iminiums

Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada
Author to whom correspondence should be addressed.
Received: 10 September 2012 / Revised: 27 September 2012 / Accepted: 27 September 2012 / Published: 11 October 2012
(This article belongs to the Special Issue Enzyme Optimization and Immobilization)
View Full-Text   |   Download PDF [4638 KB, uploaded 19 June 2014]   |  


Ornithine cyclodeaminase (OCD) is an NAD+-dependent deaminase that is found in bacterial species such as Pseudomonas putida. Importantly, it catalyzes the direct conversion of the amino acid L-ornithine to L-proline. Using molecular dynamics (MD) and a hybrid quantum mechanics/molecular mechanics (QM/MM) method in the ONIOM formalism, the catalytic mechanism of OCD has been examined. The rate limiting step is calculated to be the initial step in the overall mechanism: hydride transfer from the L-ornithine’s Cα–H group to the NAD+ cofactor with concomitant formation of a Cα=NH2+ Schiff base with a barrier of 90.6 kJ mol−1. Importantly, no water is observed within the active site during the MD simulations suitably positioned to hydrolyze the Cα=NH2+ intermediate to form the corresponding carbonyl. Instead, the reaction proceeds via a non-hydrolytic mechanism involving direct nucleophilic attack of the δ-amine at the Cα-position. This is then followed by cleavage and loss of the α-NH2 group to give the Δ1-pyrroline-2-carboxylate that is subsequently reduced to L-proline.
Keywords: OCD; L-proline; crystallin; oxidative deamination; iminium OCD; L-proline; crystallin; oxidative deamination; iminium

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Ion, B.F.; Bushnell, E.A.C.; Luna, P.D.; Gauld, J.W. A Molecular Dynamics (MD) and Quantum Mechanics/Molecular Mechanics (QM/MM) Study on Ornithine Cyclodeaminase (OCD): A Tale of Two Iminiums. Int. J. Mol. Sci. 2012, 13, 12994-13011.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top