|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6qxa' size='340' side='right'caption='[[6qxa]], [[Resolution|resolution]] 3.41Å' scene=''> | | <StructureSection load='6qxa' size='340' side='right'caption='[[6qxa]], [[Resolution|resolution]] 3.41Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6qxa]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Thema Thema]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QXA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6qxa]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermotoga_maritima_MSB8 Thermotoga maritima MSB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QXA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2PN:IMIDODIPHOSPHORIC+ACID'>2PN</scene>, <scene name='pdbligand=D1D:(4S,5S)-1,2-DITHIANE-4,5-DIOL'>D1D</scene>, <scene name='pdbligand=GQB:~{N}-[(2-azanyl-3~{H}-1,3-benzothiazol-6-yl)methyl]-1~{H}-indole-2-carboxamide'>GQB</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PN:IMIDODIPHOSPHORIC+ACID'>2PN</scene>, <scene name='pdbligand=D1D:(4S,5S)-1,2-DITHIANE-4,5-DIOL'>D1D</scene>, <scene name='pdbligand=GQB:~{N}-[(2-azanyl-3~{H}-1,3-benzothiazol-6-yl)methyl]-1~{H}-indole-2-carboxamide'>GQB</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ht3|6ht3]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6qxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qxa OCA], [https://pdbe.org/6qxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qxa RCSB], [https://www.ebi.ac.uk/pdbsum/6qxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qxa ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hppA, TM_0174 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243274 THEMA])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qxa OCA], [http://pdbe.org/6qxa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qxa RCSB], [http://www.ebi.ac.uk/pdbsum/6qxa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qxa ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HPPA_THEMA 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]<ref>PMID:11343697</ref> <ref>PMID:17605473</ref> <ref>PMID:22837527</ref> | + | [https://www.uniprot.org/uniprot/HPPA_THEMA 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]<ref>PMID:11343697</ref> <ref>PMID:17605473</ref> <ref>PMID:22837527</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 23: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thema]] | + | [[Category: Thermotoga maritima MSB8]] |
| - | [[Category: Goldman, A]] | + | [[Category: Goldman A]] |
| - | [[Category: Vidilaseris, K]] | + | [[Category: Vidilaseris K]] |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Membrane-bound pyrophosphatase]]
| + | |
| Structural highlights
6qxa is a 4 chain structure with sequence from Thermotoga maritima MSB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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 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 Thermotoga maritima 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 beta-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.
Asymmetry in catalysis by Thermotoga maritima membrane-bound pyrophosphatase demonstrated by a nonphosphorus allosteric inhibitor.,Vidilaseris K, Kiriazis A, Turku A, Khattab A, Johansson NG, Leino TO, Kiuru PS, Boije Af Gennas G, Meri S, Yli-Kauhaluoma J, Xhaard H, Goldman A Sci Adv. 2019 May 22;5(5):eaav7574. doi: 10.1126/sciadv.aav7574. eCollection 2019, May. PMID:31131322[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
- ↑ Vidilaseris K, Kiriazis A, Turku A, Khattab A, Johansson NG, Leino TO, Kiuru PS, Boije Af Gennas G, Meri S, Yli-Kauhaluoma J, Xhaard H, Goldman A. Asymmetry in catalysis by Thermotoga maritima membrane-bound pyrophosphatase demonstrated by a nonphosphorus allosteric inhibitor. Sci Adv. 2019 May 22;5(5):eaav7574. doi: 10.1126/sciadv.aav7574. eCollection 2019, May. PMID:31131322 doi:http://dx.doi.org/10.1126/sciadv.aav7574
|
