Open AccessMechanism of O2 diffusion and reduction in FeFe hydrogenases
Author(s) -
Adam Kubas,
Christophe Orain,
David De Sancho,
Laure Saujet,
Matteo Sensi,
Charles Gauquelin,
Isabelle Meynial-Salles,
Philippe Soucaille,
Hervé Bottin,
Carole Baffert,
Vincent Fourmond,
Robert B. Best,
Jochen Blumberger,
Christophe Léger
Publication year - 2016
Publication title -
nature chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.996
H-Index - 232
eISSN - 1755-4349
pISSN - 1755-4330
DOI - 10.1038/nchem.2592
Subject(s) - hydrogenase , chemistry , electron transfer , mutagenesis , active site , electron transport chain , redox , metalloprotein , photochemistry , combinatorial chemistry , enzyme , mutant , biochemistry , inorganic chemistry , gene
FeFe hydrogenases are the most efficient H 2 -producing enzymes. However, inactivation by O 2 remains an obstacle that prevents them being used in many biotechnological devices. Here, we combine electrochemistry, site-directed mutagenesis, molecular dynamics and quantum chemical calculations to uncover the molecular mechanism of O 2 diffusion within the enzyme and its reactions at the active site. We propose that the partial reversibility of the reaction with O 2 results from the four-electron reduction of O 2 to water. The third electron/proton transfer step is the bottleneck for water production, competing with formation of a highly reactive OH radical and hydroxylated cysteine. The rapid delivery of electrons and protons to the active site is therefore crucial to prevent the accumulation of these aggressive species during prolonged O 2 exposure. These findings should provide important clues for the design of hydrogenase mutants with increased resistance to oxidative damage.