Open AccessSelective cysteine-to-selenocysteine changes in a [NiFe]-hydrogenase confirm a special position for catalysis and oxygen tolerance
Author(s) -
Rhian M. Evans,
Natalie Krahn,
Bonnie J. Murphy,
Harrison Lee,
Fräser A. Armstrong,
Dieter Söll
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2100921118
Subject(s) - selenocysteine , hydrogenase , cysteine , chemistry , active site , stereochemistry , enzyme , biochemistry
Significance Substitution of cysteine by selenocysteine is held responsible for the increased performance of many enzymes: The higher activity of [NiFeSe]-hydrogenases compared with their [NiFe] counterparts is often attributed to the Sec replacement of one active-site cysteine ligand. Replacing each of the four active-site cysteine residues in an O2 -tolerant [NiFe]-hydrogenase by selenocysteine shows that this substitution alone does not overcome the inability to evolve H2 that is a characteristic of the group 1d hydrogenases. A nonbridging cysteine lying on the direct path between the Ni and an adjacent proton-relaying glutamic acid emerges as being very special: Its substitution by selenocysteine confers extreme tolerance to O2 but disrupts the proton transfer pathway, providing an example of where sulfur is superior to selenium.