title: Structural features of [NiFeSe] and [NiFe] hydrogenases determining their different properties: a computational approach.
abstract: Hydrogenases are metalloenzymes that catalyze the reversible reaction H(2)<->2H(+) + 2e(-), being potentially useful in H(2) production or oxidation. [NiFeSe] hydrogenases are a particularly interesting subgroup of the [NiFe] class that exhibit tolerance to O(2) inhibition and produce more H(2) than standard [NiFe] hydrogenases. However, the molecular determinants responsible for these properties remain unknown. Hydrophobic pathways for H(2) diffusion have been identified in [NiFe] hydrogenases, as have proton transfer pathways, but they have never been studied in [NiFeSe] hydrogenases. Our aim was, for the first time, to characterize the H(2) and proton pathways in a [NiFeSe] hydrogenase and compare them with those in a standard [NiFe] hydrogenase. We performed molecular dynamics simulations of H(2) diffusion in the [NiFeSe] hydrogenase from Desulfomicrobium baculatum and extended previous simulations of the [NiFe] hydrogenase from Desulfovibrio gigas (Teixeira et al. in Biophys J 91:2035-2045, 2006). The comparison showed that H(2) density near the active site is much higher in [NiFeSe] hydrogenase, which appears to have an alternative route for the access of H(2) to the active site. We have also determined a possible proton transfer pathway in the [NiFeSe] hydrogenase from D. baculatum using continuum electrostatics and Monte Carlo simulation and compared it with the proton pathway we found in the [NiFe] hydrogenase from D. gigas (Teixeira et al. in Proteins 70:1010-1022, 2008). The residues constituting both proton transfer pathways are considerably different, although in the same region of the protein. These results support the hypothesis that some of the special properties of [NiFeSe] hydrogenases could be related to differences in the H(2) and proton pathways.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: Carla S A
authors.initials: CS
authors.lastname: Baltazar
authors.forename: Vitor H
authors.initials: VH
authors.lastname: Teixeira
authors.forename: Cláudio M
authors.initials: CM
authors.lastname: Soares
mesh_terms: D019295:Computational Biology; D018360:Crystallography, X-Ray; D006859:Hydrogen / Q000737:chemistry; D006864:Hydrogenase / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation
chemical_list: D006859:Hydrogen; C043296:nickel-iron hydrogenase; C058560:nickel-iron-selenium hydrogenase; D006864:Hydrogenase