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Science. 2015 Jan 9;347(6218):178-81. doi: 10.1126/science.1260451.

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

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.
3
National Resource for Automated Molecular Microscopy, The Scripps Research Institute, La Jolla, CA 92037, USA.
4
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. dave@scripps.edu.

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.

PMID:
25574024
PMCID:
PMC4479213
DOI:
10.1126/science.1260451
[Indexed for MEDLINE]
Free PMC Article

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