Structural highlights
Function
HPPA_THEMA Sodium pump that utilizes the energy of pyrophosphate hydrolysis as the driving force for Na(+) movement across the membrane.[HAMAP-Rule:MF_01129][1] [2] [3]
Publication Abstract from PubMed
Membrane-bound pyrophosphatases (M-PPases), which couple proton/sodium ion transport to pyrophosphate synthesis/hydrolysis, are important in abiotic stress resistance and in the infectivity of protozoan parasites. Here, three M-PPase structures in different catalytic states show that closure of the substrate-binding pocket by helices 5-6 affects helix 13 in the dimer interface and causes helix 12 to move down. This springs a 'molecular mousetrap', repositioning a conserved aspartate and activating the nucleophilic water. Corkscrew motion at helices 6 and 16 rearranges the key ionic gate residues and leads to ion pumping. The pumped ion is above the ion gate in one of the ion-bound structures, but below it in the other. Electrometric measurements show a single-turnover event with a non-hydrolysable inhibitor, supporting our model that ion pumping precedes hydrolysis. We propose a complete catalytic cycle for both proton and sodium-pumping M-PPases, and one that also explains the basis for ion specificity.
Membrane pyrophosphatases from Thermotoga maritima and Vigna radiata suggest a conserved coupling mechanism.,Li KM, Wilkinson C, Kellosalo J, Tsai JY, Kajander T, Jeuken LJ, Sun YJ, Goldman A Nat Commun. 2016 Dec 6;7:13596. doi: 10.1038/ncomms13596. PMID:27922000[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Perez-Castineira JR, Lopez-Marques RL, Losada M, Serrano A. A thermostable K(+)-stimulated vacuolar-type pyrophosphatase from the hyperthermophilic bacterium Thermotoga maritima. FEBS Lett. 2001 May 4;496(1):6-11. PMID:11343697
- ↑ Malinen AM, Belogurov GA, Baykov AA, Lahti R. Na+-pyrophosphatase: a novel primary sodium pump. Biochemistry. 2007 Jul 31;46(30):8872-8. Epub 2007 Jul 3. PMID:17605473 doi:http://dx.doi.org/10.1021/bi700564b
- ↑ Kellosalo J, Kajander T, Kogan K, Pokharel K, Goldman A. The structure and catalytic cycle of a sodium-pumping pyrophosphatase. Science. 2012 Jul 27;337(6093):473-6. PMID:22837527 doi:10.1126/science.1222505
- ↑ Li KM, Wilkinson C, Kellosalo J, Tsai JY, Kajander T, Jeuken LJ, Sun YJ, Goldman A. Membrane pyrophosphatases from Thermotoga maritima and Vigna radiata suggest a conserved coupling mechanism. Nat Commun. 2016 Dec 6;7:13596. doi: 10.1038/ncomms13596. PMID:27922000 doi:http://dx.doi.org/10.1038/ncomms13596
