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Protein Film Infrared Electrochemistry Demonstrated for Study of H2 Oxidation by a [NiFe] Hydrogenase
Published on: December 4, 2017
Discovery and characterization of a nickel enzyme family that catalyses intermolecular hydride shuttling
Zoë L Semersky1, Conor G Raymond1, John M Rossi1
1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Abstract:
Nickel-dependent enzymes catalyse incredible transformations. However, few have been discovered so far, limiting our understanding of the role of nickel in nature. Here we develop a bioinformatic pipeline to discover a family of nickel pincer mononucleotide (NPMN)-dependent enzymes with structures that are completely distinct from previously reported NPMN-dependent enzymes. We characterize one family member, NPMN-dependent hydride transferase (NphT), and find that it catalyses intermolecular hydride transfer, which we elucidate through its promiscuous disproportionation of sugars. We solve a 1.3-Å resolution crystal structure of NphT bound to NPMN and interrogate its mechanism through mutagenesis. We discover that NphT is one of many unexplored nickel enzymes within the large aldo-keto reductase superfamily, which catalyses reactions on a wide range of molecules, including secondary metabolites, sugars and drugs. This work reveals a unique enzymatic scaffold that can harness nickel, expands the known NPMN-catalysed transformations to intermolecular hydride transfer and establishes a pipeline for the discovery of distinct families of nickel-dependent enzymes.
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