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  The Hydride Transfer Process in NADP-dependent Methylene-tetrahydromethanopterin Dehydrogenase

Huang, G., Wagner, T., Demmer, U., Warkentin, E., Ermler, U., & Shima, S. (2020). The Hydride Transfer Process in NADP-dependent Methylene-tetrahydromethanopterin Dehydrogenase. Journal of Molecular Biology (London), 432(7), 2042-2054. doi:10.1016/j.jmb.2020.01.042.

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 Creators:
Huang, Gangfeng1, Author
Wagner, Tristan1, 2, Author
Demmer, Ulrike3, Author              
Warkentin, Eberhard3, Author              
Ermler, Ulrich3, Author              
Shima, Seigo1, Author
Affiliations:
1Max-Planck-Institut für Terrestrische Mikrobiologie, Karl-von-Frisch Straße 10, 35043 Marburg, Germany, ou_persistent22              
2Max-Planck-Institut für Marine Mikrobiologie, Celsiusstraße 1, 28359 Bremen, Germany, ou_persistent22              
3Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max Planck Society, ou_2068290              

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Free keywords: conformational changes; dehydrogenase; enzyme catalysis; one-carbon metabolism; X-ray crystallography
 Abstract: NADP-dependent methylene-tetrahydromethanopterin (methylene-H4MPT) dehydrogenase (MtdA) catalyzes the reversible dehydrogenation of methylene-H4MPT to form methenyl-H4MPT+ by using NADP+ as a hydride acceptor. This hydride transfer reaction is involved in the oxidative metabolism from formaldehyde to CO2 in methylotrophic and methanotrophic bacteria. Here, we report on the crystal structures of the ternary MtdA-substrate complexes from Methylorubrum extorquens AM1 obtained in open and closed forms. Their conversion is accomplished by opening/closing the active site cleft via a 15° rotation of the NADP, relative to the pterin domain. The 1.08 Å structure of the closed and active enzyme-NADP+−methylene-H4MPT complex allows a detailed geometric analysis of the bulky substrates and a precise prediction of the hydride trajectory. Upon domain closure, the bulky substrate rings become compressed resulting in a tilt of the imidazolidine group of methylene-H4MPT that optimizes the geometry for hydride transfer. An additional 1.5 Å structure of MtdA in complex with the nonreactive NADP+ and methenyl-H4MPT+ revealed an extremely short distance between nicotinamide-C4 and imidazoline-C14a of 2.5 Å, which demonstrates the strong pressure imposed. The pterin-imidazolidine-phenyl butterfly angle of methylene-H4MPT bound to MtdA is smaller than that in the enzyme-free state but is similar to that in H2- and F420-dependent methylene-H4MPT dehydrogenases. The concept of compression-driven hydride transfer including quantum mechanical hydrogen tunneling effects, which are established for flavin- and NADP-dependent enzymes, can be expanded to hydride-transferring H4MPT-dependent enzymes

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Language(s): eng - English
 Dates: 2020-01-242019-12-042020-01-282020-02-132020-03-27
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.jmb.2020.01.042
 Degree: -

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Title: Journal of Molecular Biology (London)
  Other : J Mol Biol
Source Genre: Journal
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Publ. Info: London : Academic Press
Pages: 13 Volume / Issue: 432 (7) Sequence Number: - Start / End Page: 2042 - 2054 Identifier: ISSN: 0022-2836
CoNE: https://pure.mpg.de/cone/journals/resource/954922646042