title: New insights into the reaction capabilities of His195adjacent to the active site of nitrogenase.
abstract: The active site of the enzyme nitrogenase is the FeMo-cofactor (FeMo-co), a C-centred Fe7MoS9cluster, connected to the surrounding MoFe protein via ligands Cys275and His442. Density functional calculations, involving 14 additional surrounding amino acids, focus on His195because its mutation causes important reactivity changes, including almost complete loss of ability to reduce N2to NH3. The Nε side-chain of His195is capable of hydrogen bonding to S2B, bridging Fe2 and Fe6 of FeMo-co, believed to be the main reaction domain of nitrogenase. Details are presented for the possible ways in which protonated or deprotonated Nε of His195interact with S2B or S2B-H or Fe2 or Fe2-H or Fe-(H2). Movements of the His195side-chain allow formation of a significant short dihydrogen bond between Nε of His195and H on Fe2: Nε-H••H-Fe2, with H-H=1.39Å. It is shown that a 180° rotation of the imidazole ring of His195is not able to facilitate transfer of protons from the protein surface to FeMo-co. His195is able to move H atoms to and from S2B, and the characteristics of H transfer between S2B and Nε of His195are described, together with their dependence on the protonation state of His195and the redox state of FeMo-co. The water molecule on the posterior Nδ side of His195can mediate proton transfer to and from the side-chain of Tyr228. The accumulated results suggest that protonated His195could be the agent for the first, most difficult, transfer of H to bound substrate N2.
authors.affiliation: School of Chemistry, UNSW Australia, Sydney, 2052, Australia. Electronic address: i.dance@unsw.edu.au.
authors.forename: Ian
authors.initials: I
authors.lastname: Dance
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D006632:Histamine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008983:Molybdoferredoxin / Q000737:chemistry* / Q000378:metabolism*; D009591:Nitrogenase / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008983:Molybdoferredoxin; D006632:Histamine; D009591:Nitrogenase
keywords: Density functional calculations; Dihydrogen bond; FeMo-co; Hydrogen bond; Mechanism; Nitrogenase