Structural biology. Division of labor in transhydrogenase by alternating proton translocation and hydride transfer.
Publication Type:Journal Article
Source:Science, Volume 347, Issue 6218, p.178-81 (2015)
Keywords:Amino Acid Sequence, Crystallography, X-Ray, Molecular Sequence Data, NADP Transhydrogenases, Protein Multimerization, Protein Structure, Tertiary, Protons, Thermus thermophilus
<p>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. </p>