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Modelling of the reaction mechanism of Isopropyl-malate dehydrogenase – running

The isopropyl-malate dehydrogenase enzyme plays an essential role in the leucine biosynthesis pathways of bacteria, which is vital for the survival of these organisms. As such it may provide a new target in the development of antibacterial drugs.
The enzyme catalyses the dehydrogenation of the isopropyl-malate substrate in a step-wise process, but the details of the reaction are not known, yet.
The aim of the project is to model the reaction mechanism of isopropyl-malate dehydrogenase. We would like to uncover which aminoacid residues play a key role in the proper functioning of the enzyme and to determine the barrier of the reaction catalyzed by the enzyme. For the modelling we use a newly determined X-ray structure of the enzyme, and we plan to carry out molecular dynamics simulations and combined quantum chemical molecular mechanics calculations.
We hope that our project will contribute to the understanding of the reaction mechanism not only of isopropyl-malate dehydrogenase, but to the whole class enzymes where it belongs to.

Project owner:
Dr. Oláh Julianna (Szervetlen és Analitikai Kémia Tanszék)
Members:
Szervetlen és Analitikai Kémia Tanszék (VBK-IAACHEM)
Cooperations:

Természettudományi Kutatóközpont,
Helmholtz-Zentrum Berlin für Materialien und Energie, Macromolecular Crystallography (HZB-MX), Albert-Einstein-Str. 15, D-12489 Berlin, Germany,
Universitá degli Studi di Parma, Dipartimento di Bioscienze, Viale G.P. Usberti 23/A, I-43100 Parma, Italy.