Mechanisms of enzyme catalysis and relation to enzyme dynamics

Main Research line: Protein dynamics and enzyme catalysis
Main Researcher: Ramon Crehuet

Enzymes are proteins that catalyze chemical reactions. The description of chemical reactions needs Quantum Mechanical (QM) methods, but enzymes are too big to be treated with such expensive methods. A successful solution is the use of hybrid QM/MM, where the reacting atoms are treated with QM methods and the environment with Molecular Mechanics (MM).

What we do
We use the algorithms we’ve implemented and other available methods to study several enzymatic processes.[1] In particular we have done several works on Phosphoryl transfer reactions. The ubiquity of kinases and phosphatases reveals the essential role of phosphoryl groups in biology. However, their mechanism is still highly debated.
In one of our studies, we determined the non-existence of a penta-coordinated intermediate that had presumably been observed in a crystal of beta-phosphoglucomutase. [2]We studied the N-acetilglutamate kinase, characterized by Rubio’s group in Valencia, where we have determined the role of protein motions in reducing the energy barrier for the reaction.[3]
We are currently working with a scavenger decapping enzyme to understand why some necessary motions seem to deactivate the enzyme if they happen too often. This work is done in collaboration with Remco Sprangers and Silvia Osuna.

We also work on the mechanism of several aldolases together with Pere Calpés in our institute. These enzymes catalyze the aldol reaction in a stereospecific way. The formation of new carbon-carbon bonds is useful in the synthesis of potentially bioactive compounds. The use of enzymes guarantees a green approach to chemical synthesis.[4,5]

In this line of research, we use pDynamo and Gromacs.

Compression motions of N-acetylglutamate kinase that affect catalysis produce conformations that have a lower reaction barrier

Compression motions of N-acetylglutamate kinase that affect catalysis produce conformations that have a lower reaction barrier

Related publications

Jiménez, A.; Clapés, P.; Crehuet, R, A Dynamic View of Enzyme Catalysis, J. Mol. Model, 2008, 14 (8), 35–746

Marcos, E.; Crehuet, R.; Anglada, J. M., Inductive and External Electric Field Effects in Pentacoordinated Phosphorus Compounds, J. Chem. Theory Comput, 2008, 4 (1), 49–63

Sanchez-Martinez, M.; Marcos, E.; Tauler, R.; Field, M.; Crehuet, R, Conformational Compression and Barrier Height Heterogeneity in the N-Acetylglutamate Kinase, J. Phys. Chem. B, 2013, 117 (46), 14261–14272

Jiménez, A.; Clapés, P.; Crehuet, R, Protein Flexibility and Metal Coordination Changes in DHAP-Dependent Aldolases, Chem. -Eur. J., 2009, 15 (6), 1422–1428

Garrabou, X.; Joglar, J.; Parella, T.; Crehuet, R.; Bujons, J.; Clapes, P, Redesign of the Phosphate Binding Site of L-Rhamnulose-1-Phosphate Aldolase towards a Dihydroxyacetone Dependent Aldolase, Adv. Synth. Catal., 2011, 353 (1), 89-99

If you have any questions or comments, feel free to contact us. We’ll be happy to hear from you.