Division of labor in transhydrogenase by alternating proton translocation and hydride transfer

Josephine H. Leung, Lici A. Schurig-Briccio, Mutsuo Yamaguchi, Arne Moeller, Jeffrey A. Speir, Robert B Gennis, Charles D. Stout

Research output: Contribution to journalArticle

Abstract

NADPH/NADP+ (the reduced form of NADP+/nicotinamide adenine dinucleotide phosphate) homeostasis is critical for countering oxidative stress in cells. Nicotinamide nucleotide transhydrogenase (TH), a membrane enzyme present in both bacteria and mitochondria, couples the proton motive force to the generation of NADPH.We present the 2.8 Å crystal structure of the transmembrane proton channel domain of TH from Thermus thermophilus and the 6.9 Å crystal structure of the entire enzyme (holo-TH). The membrane domain crystallized as a symmetric dimer, with each protomer containing a putative proton channel. The holo-TH is a highly asymmetric dimer with the NADP(H)-binding domain (dIII) in two different orientations. This unusual arrangement suggests a catalytic mechanism in which the two copies of dIII alternatively function in proton translocation and hydride transfer.

Original languageEnglish (US)
Pages (from-to)178-181
Number of pages4
JournalScience
Volume347
Issue number6218
DOIs
StatePublished - Jan 9 2015

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NADP
Protons
NADP Transhydrogenases
Thermus thermophilus
Proton-Motive Force
Membranes
Protein Subunits
Enzymes
Mitochondria
Oxidative Stress
Homeostasis
Bacteria

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Leung, J. H., Schurig-Briccio, L. A., Yamaguchi, M., Moeller, A., Speir, J. A., Gennis, R. B., & Stout, C. D. (2015). Division of labor in transhydrogenase by alternating proton translocation and hydride transfer. Science, 347(6218), 178-181. https://doi.org/10.1126/science.1260451

Division of labor in transhydrogenase by alternating proton translocation and hydride transfer. / Leung, Josephine H.; Schurig-Briccio, Lici A.; Yamaguchi, Mutsuo; Moeller, Arne; Speir, Jeffrey A.; Gennis, Robert B; Stout, Charles D.

In: Science, Vol. 347, No. 6218, 09.01.2015, p. 178-181.

Research output: Contribution to journalArticle

Leung, JH, Schurig-Briccio, LA, Yamaguchi, M, Moeller, A, Speir, JA, Gennis, RB & Stout, CD 2015, 'Division of labor in transhydrogenase by alternating proton translocation and hydride transfer', Science, vol. 347, no. 6218, pp. 178-181. https://doi.org/10.1126/science.1260451
Leung JH, Schurig-Briccio LA, Yamaguchi M, Moeller A, Speir JA, Gennis RB et al. Division of labor in transhydrogenase by alternating proton translocation and hydride transfer. Science. 2015 Jan 9;347(6218):178-181. https://doi.org/10.1126/science.1260451
Leung, Josephine H. ; Schurig-Briccio, Lici A. ; Yamaguchi, Mutsuo ; Moeller, Arne ; Speir, Jeffrey A. ; Gennis, Robert B ; Stout, Charles D. / Division of labor in transhydrogenase by alternating proton translocation and hydride transfer. In: Science. 2015 ; Vol. 347, No. 6218. pp. 178-181.
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