title: Insights into catalytic activity of industrial enzyme Co-nitrile hydratase. Docking studies of nitriles and amides.
abstract: Nitrile hydratase (NHase) is an enzyme containing non-corrin Co3+ in the non-standard active site. NHases from Pseudonocardia thermophila JCM 3095 catalyse hydration of nitriles to corresponding amides. The efficiency of the enzyme is 100 times higher for aliphatic nitriles then aromatic ones. In order to understand better this selectivity dockings of a series of aliphatic and aromatic nitriles and related amides into a model protein based on an X-ray structure were performed. Substantial differences in binding modes were observed, showing better conformational freedom of aliphatic compounds. Distinct interactions with postranslationally modified cysteines present in the active site of the enzyme were observed. Modeling shows that water molecule activated by a metal ion may easily directly attack the docked acrylonitrile to transform this molecule into acryloamide. Thus docking studies provide support for one of the reaction mechanisms discussed in the literature.
authors.affiliation: Theoretical Molecular Biophysics Group, Institute of Physics, N. Copernicus University, Grudziadzka 5, 87-100, Torun, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Peplowski
authors.forename: Karina
authors.initials: K
authors.lastname: Kubiak
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Nowak
mesh_terms: D000192:Actinomycetales / Q000201:enzymology; D000465:Algorithms; D000577:Amides / Q000737:chemistry*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D003035:Cobalt / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D006836:Hydro-Lyases / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D008970:Molecular Weight; D009570:Nitriles / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry
chemical_list: D000577:Amides; D009570:Nitriles; D021122:Protein Subunits; D014867:Water; D003035:Cobalt; D006836:Hydro-Lyases; C048831:nitrile hydratase; D003545:Cysteine