6QXA

Structure of membrane bound pyrophosphatase from Thermotoga maritima in complex with imidodiphosphate and N-[(2-amino-6-benzothiazolyl)methyl]-1H-indole-2-carboxamide (ATC)

Summary for 6QXA

• Entry DOI: 10.2210/pdb6qxa/pdb
• Descriptor: K(+)-stimulated pyrophosphate-energized sodium pump, MAGNESIUM ION, IMIDODIPHOSPHORIC ACID, ... (8 entities in total)
• Functional Keywords: membrane-bound pyrophosphatase, inhibitor, membrane protein
• Biological source: Thermotoga maritima MSB8
• Total number of polymer chains: 4
• Total formula weight: 315374.32

Authors

Vidilaseris, K.,Goldman, A. (deposition date: 2019-03-07, release date: 2019-04-10, Last modification date: 2024-02-07)

Primary citation

Vidilaseris, K.,Kiriazis, A.,Turku, A.,Khattab, A.,Johansson, N.G.,Leino, T.O.,Kiuru, P.S.,Boije Af Gennas, G.,Meri, S.,Yli-Kauhaluoma, J.,Xhaard, H.,Goldman, A.
Asymmetry in catalysis byThermotoga maritimamembrane-bound pyrophosphatase demonstrated by a nonphosphorus allosteric inhibitor.
Sci Adv, 5:eaav7574-eaav7574, 2019

PubMed Abstract: Membrane-bound pyrophosphatases are homodimeric integral membrane proteins that hydrolyze pyrophosphate into orthophosphates, coupled to the active transport of protons or sodium ions across membranes. They are important in the life cycle of bacteria, archaea, plants, and parasitic protists, but no homologous proteins exist in vertebrates, making them a promising drug target. Here, we report the first nonphosphorus allosteric inhibitor of the thermophilic bacterium membrane-bound pyrophosphatase and its bound structure together with the substrate analog imidodiphosphate. The unit cell contains two protein homodimers, each binding a single inhibitor dimer near the exit channel, creating a hydrophobic clamp that inhibits the movement of β-strand 1-2 during pumping, and thus prevents the hydrophobic gate from opening. This asymmetry of inhibitor binding with respect to each homodimer provides the first clear structural demonstration of asymmetry in the catalytic cycle of membrane-bound pyrophosphatases.

PubMed: 31131322
DOI: 10.1126/sciadv.aav7574

Experimental method

X-RAY DIFFRACTION (3.41 Å)