sept. 2011

New paper out: Enzyme Closure and Nucleotide Binding Structurally Lock Guanylate Kinase

We investigate the conformational dynamics and mechanical properties of guanylate kinase (GK) using a multiscale approach combining high-resolution atomistic molecular dynamics and low-resolution Brownian dynamics simulations. The GK enzyme is subject to large conformational changes, leading from an open to a closed form, which are further influenced by the presence of nucleotides. As suggested by recent work on simple coarse-grained models of apo-GK, we primarily focus on GK's closure mechanism with the aim to establish a detailed picture of the hierarchy and chronology of structural events essential for the enzymatic reaction. We have investigated open-versus-closed, apo-versus-holo, and substrate-versus-product-loaded forms of the GK enzyme. Bound ligands significantly modulate the mechanical and dynamical properties of GK and rigidity profiles of open and closed states hint at functionally important differences. Our data emphasizes the role of magnesium, highlights a water channel permitting active site hydration, and reveals a structural lock that stabilizes the closed form of the enzyme.
By Olivier Delalande, Sophie Sacquin-Mora and Marc Baaden, published in Biophysical Journal Volume 101, Issue 6, 1440-1449, 21 September 2011.

Welcome Samuel, Francesco and Antoine

Welcome to Samuel Murail, Francesco Oteri and Antoine Taly who have just arrived in the lab. Samuel will be working as a post-doc on the Nico_chimera project. Francesco is also carrying out post-doctoral research in the BioPac project. Antoine has previously been in Strasbourg and has joined our lab as a CNRS researcher and expert in channels and receptors.