4O9T

Mechanism of transhydrogenase coupling proton translocation and hydride transfer

Summary for 4O9T

• Entry DOI: 10.2210/pdb4o9t/pdb
• Descriptor: NAD(P) transhydrogenase subunit alpha 2, NAD(P) transhydrogenase subunit beta (2 entities in total)
• Functional Keywords: nicotinamide nucleotide transhydrogenase couples the proton motive force to nadph formation, integral membrane component of thermus thermophilus transhydrogenase, respiratory enzyme, protons and nad(h), nadp(h), proton translocation and hydride transfer, periplasmic membrane and cytosol, membrane protein
• Biological source: Thermus thermophilus; More
• Total number of polymer chains: 8
• Total formula weight: 160618.81

Authors

Leung, J.H.,Yamaguchi, M.,Moeller, A.,Schurig-Briccio, L.A.,Gennis, R.B.,Potter, C.S.,Carragher, B.,Stout, C.D. (deposition date: 2014-01-02, release date: 2014-06-11, Last modification date: 2024-02-28)

Primary citation

Leung, J.H.,Schurig-Briccio, L.A.,Yamaguchi, M.,Moeller, A.,Speir, J.A.,Gennis, R.B.,Stout, C.D.
Structural biology. Division of labor in transhydrogenase by alternating proton translocation and hydride transfer.
Science, 347:178-181, 2015

PubMed 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.

PubMed: 25574024
DOI: 10.1126/science.1260451

Experimental method

X-RAY DIFFRACTION (3.079 Å)