The direct role of selenocysteine in [NiFeSe] hydrogenase maturation and catalysis.
Marques, M.C., Tapia, C., Gutierrez-Sanz, O., Ramos, A.R., Keller, K.L., Wall, J.D., De Lacey, A.L., Matias, P.M., Pereira, I.A.C.(2017) Nat Chem Biol 13: 544-550
- PubMed: 28319099 
- DOI: https://doi.org/10.1038/nchembio.2335
- Primary Citation of Related Structures:  
5JSH, 5JSK, 5JSU, 5JSY, 5JT1 - PubMed Abstract: 
Hydrogenases are highly active enzymes for hydrogen production and oxidation. [NiFeSe] hydrogenases, in which selenocysteine is a ligand to the active site Ni, have high catalytic activity and a bias for H 2 production. In contrast to [NiFe] hydrogenases, they display reduced H 2 inhibition and are rapidly reactivated after contact with oxygen. Here we report an expression system for production of recombinant [NiFeSe] hydrogenase from Desulfovibrio vulgaris Hildenborough and study of a selenocysteine-to-cysteine variant (Sec489Cys) in which, for the first time, a [NiFeSe] hydrogenase was converted to a [NiFe] type. This modification led to severely reduced Ni incorporation, revealing the direct involvement of this residue in the maturation process. The Ni-depleted protein could be partly reconstituted to generate an enzyme showing much lower activity and inactive states characteristic of [NiFe] hydrogenases. The Ni-Sec489Cys variant shows that selenium has a crucial role in protection against oxidative damage and the high catalytic activities of the [NiFeSe] hydrogenases.
Organizational Affiliation: 
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.