Substrate selectivity and conformational space available to bromoxynil and acrylonitrile in iron nitrile hydratase

Dalton Transactions : an International Journal of Inorganic Chemistry
Lopa V Desai, M Zimmer

Abstract

Nitrile hydratase (NHase) is used in the commercial conversion of acrylonitrile to acrylamide. There are two main types of NHase: the iron containing and the cobalt containing NHase. They catalyze the conversion of a wide variety of nitriles to their corresponding amides. The Co-NHases are more robust and have wider substrate specificity than the Fe-NHase. We have used dihedral and positional variational Monte Carlo conformational searches to determine the conformational space available to acrylonitrile and bromoxynil bound to the iron in the active site of NHase. Dioxane is an Fe-NHase inhibitor, but has no effect on Co-NHase activity. Our conformational searches showed that although the dioxane restricts the conformational freedom of the iron coordinated acrylonitrile, there is enough room in the active site for both the acrylonitrile and dioxane. A conformational search of dioxane in the active site of Fe-NHase, in the absence of a substrate, revealed that the acrylonitrile and dioxane do not share the same space. We have also shown that if the function of the metal ions in NHases is to activate the nitrile by binding to it and acting as a Lewis acid, then the entrance and channel residues are most likely responsible for Fe-...Continue Reading

Citations

Feb 1, 2008·Biophysical Journal·Karina Kubiak, Wieslaw Nowak
Aug 2, 2011·Metallomics : Integrated Biometal Science·Sachi Okamoto, Lindsay D Eltis
Apr 17, 2013·The Journal of Biological Chemistry·Natalie GumataotaoRichard C Holz
Dec 8, 2006·The Journal of Biological Chemistry·Sanghamitra Mitra, Richard C Holz
Sep 2, 2021·Journal of Agricultural and Food Chemistry·Shilei SunMiaomiao Sheng

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