Understanding the Special Properties of [NiFeSe] Hydrogenases through the Use of Computational Methodologies

Abstract

Hydrogenases are metalloenzymes that catalyze the reversible reaction H2 ⇄ 2H+ +2e- . In order to use H2 as fuel in a sustainable way, we should learn how to use hydrogenases' unique ability to oxidize and produce H2 without the need for high temperatures, high over potentials and noble metals.Two main families of hydrogenases can be distinguished: the [FeFe] and the [NiFe] hydrogenases. Among the last ones, there is a subgroup with outstanding properties - the [NiFeSe] hydrogenases. They have higher activities and are less inhibited by product during H2 production, and they are more tolerant to the inhibition by O2 than the standard [NiFe] hydrogenases. However, the structural determinants responsible for these special properties remain unknown. The replacement of the one of the active site cysteines by a selenocysteine, apparently, is not enough to explain the differences between the standard [NiFe] and the [NiFeSe] hydrogenases. In addition, it is also not understood, why some [NiFeSe] hydrogenases can exist in a membrane form and in a soluble form, and why is the membrane form more active when the only difference between them is a lipidic tail for membrane anchoring.Our aim is to the answer the open questions regarding the special features of [NiFeSe] hydrogenases using computational methodologies such as molecular dynamics and continuum electrostatics. Our first results indicate that the [NiFeSe] hydrogenases have an alternative channel for H2 diffusion between the protein exterior and the deeply buried active site non-existing in standard [NiFe] hydrogenases. We have also been able to identify differences in the proton transfer pathways between the two types of hydrogenases.