Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.600271
Title: Transhydrogenase : understanding a molecular machine
Author: Matharu, Parvitar
ISNI:       0000 0004 5350 5483
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2014
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Abstract:
Transhydrogenase couples hydride transfer between NADH and NADP+ to proton translocation across a membrane in animal mitochondria and bacteria. The product/reactant ratio can be driven to values greater than 400 by the energy of the proton gradient, demonstrating the importance of this gradient, and hence why transhydrogenase can be considered a molecular machine. We isolated a number of possible transition states for the hydride transfer reaction in R. rubrum transhydrogenase, the lowest energy of which is symmetrical. The nicotinamide ring orientation observed in the enzyme crystal structure most closely resembles an isolated asymmetrical transition state, not a symmetrical one. This observation is the basis for the asymmetric hypothesis. The asymmetric transition state hypothesis postulates that the asymmetry of the hydride transfer transition state for the reaction is responsible for the raised equilibrium constant. We set out to probe the thermodynamics of the hydride transfer reaction using hybrid QM/MM (ONIOM) calculations on simple dIdIII model systems of R. rubrum transhydrogenase. Our results with these simple model systems allow us to infer that the whilst the asymmetry of the transition state is influential in altering the equilibrium constant of the hydride transfer reaction, the binding interactions of the surrounding protein environment also play a significant role.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.600271  DOI: Not available
Keywords: QD Chemistry
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