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

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

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Received: 10 September 2012; in revised form: 27 September 2012 / Accepted: 27 September 2012 / Published: 11 October 2012
(This article belongs to the Special Issue Enzyme Optimization and Immobilization)
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Abstract: 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

AMA Style

Ion BF, Bushnell EAC, Luna PD, Gauld JW. A Molecular Dynamics (MD) and Quantum Mechanics/Molecular Mechanics (QM/MM) Study on Ornithine Cyclodeaminase (OCD): A Tale of Two Iminiums. International Journal of Molecular Sciences. 2012; 13(10):12994-13011.

Chicago/Turabian Style

Ion, Bogdan F.; Bushnell, Eric A. C.; Luna, Phil De; Gauld, James W. 2012. "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. 13, no. 10: 12994-13011.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert