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| | <StructureSection load='5jwb' size='340' side='right'caption='[[5jwb]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='5jwb' size='340' side='right'caption='[[5jwb]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jwb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JWB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JWB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jwb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JWB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CXS:3-CYCLOHEXYL-1-PROPYLSULFONIC+ACID'>CXS</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=TRT:FRAGMENT+OF+TRITON+X-100'>TRT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jwc|5jwc]], [[5jwa|5jwa]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CXS:3-CYCLOHEXYL-1-PROPYLSULFONIC+ACID'>CXS</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=TRT:FRAGMENT+OF+TRITON+X-100'>TRT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF3D7_0915000 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=5jwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jwb OCA], [https://pdbe.org/5jwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jwb RCSB], [https://www.ebi.ac.uk/pdbsum/5jwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jwb ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NADH:ubiquinone_reductase_(H(+)-translocating) NADH:ubiquinone reductase (H(+)-translocating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.3 1.6.5.3] </span></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=5jwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jwb OCA], [http://pdbe.org/5jwb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jwb RCSB], [http://www.ebi.ac.uk/pdbsum/5jwb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jwb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q8I302_PLAF7 Q8I302_PLAF7] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plaf7]] | + | [[Category: Plasmodium falciparum 3D7]] |
| - | [[Category: Li, X L]] | + | [[Category: Li XL]] |
| - | [[Category: Yu, Y]] | + | [[Category: Yu Y]] |
| - | [[Category: Membrane protein-inhibitor complex]]
| + | |
| - | [[Category: Nadh]]
| + | |
| - | [[Category: Pfndh2]]
| + | |
| Structural highlights
5jwb is a 2 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.7Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q8I302_PLAF7
Publication Abstract from PubMed
Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) represents a viable target for antimalarial drug development. However, the absence of structural information on PfNDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the PfNDH2 protein for the first time in Apo-, NADH-, and RYL-552 (a new inhibitor)-bound states. The PfNDH2 inhibitor exhibits excellent potency against both drug-resistant strains in vitro and parasite-infected mice in vivo via a potential allosteric mechanism. Furthermore, it was found that the inhibitor can be used in combination with dihydroartemisinin (DHA) synergistically. These findings not only are important for malarial PfNDH2 protein-based drug development but could also have broad implications for other NDH2-containing pathogenic microorganisms such as Mycobacterium tuberculosis.
Target Elucidation by Cocrystal Structures of NADH-Ubiquinone Oxidoreductase of Plasmodium falciparum (PfNDH2) with Small Molecule To Eliminate Drug-Resistant Malaria.,Yang Y, Yu Y, Li X, Li J, Wu Y, Yu J, Ge J, Huang Z, Jiang L, Rao Y, Yang M J Med Chem. 2017 Mar 9;60(5):1994-2005. doi: 10.1021/acs.jmedchem.6b01733. Epub, 2017 Feb 22. PMID:28195463[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yang Y, Yu Y, Li X, Li J, Wu Y, Yu J, Ge J, Huang Z, Jiang L, Rao Y, Yang M. Target Elucidation by Cocrystal Structures of NADH-Ubiquinone Oxidoreductase of Plasmodium falciparum (PfNDH2) with Small Molecule To Eliminate Drug-Resistant Malaria. J Med Chem. 2017 Mar 9;60(5):1994-2005. doi: 10.1021/acs.jmedchem.6b01733. Epub, 2017 Feb 22. PMID:28195463 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b01733
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