title: Theoretical investigation on the restoring step of the carbonic anhydrase catalytic cycle for natural and promiscuous substrates.
abstract: In the present study steered molecular dynamics simulations were applied to investigate the unbinding process of the complex of human carbonic anhydrase with the natural HCO3(-) and promiscuous H2NCOHN(-) products. This process is crucial for restoring the catalytic cycle of the enzyme. This investigation set out to give further insights on the release mechanism involved in the case of the promiscuous product believed suicide inhibitor for the hCAII against the natural final product. In particular, on the basis of the NPT molecular dynamics simulations performed on the bicarbonate, the penta-coordinated complex with the water is observed, while in the case of the ureate the same event does not take place. At this purpose the calculated potential of mean force based on the steered molecular dynamics (SMD) simulations shed light on an optimal pathway for the releasing of the products.
authors: Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P. Bucci, cubo 14c, 87036 Rende, Italy.
authors: Paolo
authors: P
authors: Piazzetta
authors: Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P. Bucci, cubo 14c, 87036 Rende, Italy.
authors: Tiziana
authors: T
authors: Marino
authors: Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P. Bucci, cubo 14c, 87036 Rende, Italy.
authors: Nino
authors: N
authors: Russo
mesh_terms: D001639:Bicarbonates / Q000378:metabolism; D055162:Biocatalysis; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D001639:Bicarbonates; D002256:Carbonic Anhydrases
keywords: Bicarbonate; Binding energy; Enzymatic catalytic turnover; SMD; Ureate; hCAII