Revealing Molecular Mechanism of the Cyclic Dimeric Guanosine Monophosphate Hydrolysis
Bella Grigorenko, Marina Knyazeva, Ekaterina Kots, Alexander Nemukhin
Molecular modeling tools including the molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) approaches are applied to understand details of the enzyme hydrolysis of an important second messenger, the cyclic dimeric guanosine monophosphate (c-di-GMP). Phosphodiesterases containing the conserved eponymous Glu-Ala-Leu (EAL) motif asymmetrically cleave the c-di-GMP into the dinucleotide species 5′-pGpG (Figure EAL-1).
Figure EAL-1. A view on the EAL domain phosphodiesterase (left) and the chemical structure of the substrate (right).
Following simulation results we suggest a molecular model (Figure EAL-2) which can be used to clarify the mechanism of c-di-GMP hydrolysis.
Figure EAL-2. A model of the active site.
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