Enzyme closure and nucleotide binding structurally lock guanylate kinase.

ABSTRACT: 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 mech

SUBMITTER: Delalande O 

PROVIDER: S-EPMC3177050 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature