4gae
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gae]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_HB3 Plasmodium falciparum HB3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GAE FirstGlance]. <br> | <table><tr><td colspan='2'>[[4gae]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_HB3 Plasmodium falciparum HB3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GAE FirstGlance]. <br> | ||
| - | </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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FOB:[(1R)-3-[ACETYL(HYDROXY)AMINO]-1-(PYRIDIN-4-YL)PROPYL]PHOSPHONIC+ACID'>FOB</scene>, <scene name='pdbligand=FOQ:[(1S)-3-[ACETYL(HYDROXY)AMINO]-1-(PYRIDIN-4-YL)PROPYL]PHOSPHONIC+ACID'>FOQ</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 2.3Å</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FOB:[(1R)-3-[ACETYL(HYDROXY)AMINO]-1-(PYRIDIN-4-YL)PROPYL]PHOSPHONIC+ACID'>FOB</scene>, <scene name='pdbligand=FOQ:[(1S)-3-[ACETYL(HYDROXY)AMINO]-1-(PYRIDIN-4-YL)PROPYL]PHOSPHONIC+ACID'>FOQ</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></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=4gae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gae OCA], [https://pdbe.org/4gae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gae RCSB], [https://www.ebi.ac.uk/pdbsum/4gae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gae ProSAT]</span></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=4gae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gae OCA], [https://pdbe.org/4gae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gae RCSB], [https://www.ebi.ac.uk/pdbsum/4gae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gae ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/DXR_PLAFX DXR_PLAFX] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).<ref>PMID:10477522</ref> | [https://www.uniprot.org/uniprot/DXR_PLAFX DXR_PLAFX] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).<ref>PMID:10477522</ref> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is a target for developing antimalarial drugs. Fosmidomycin, a potent DXR inhibitor, showed safety as well as efficacy against P. falciparum malaria in clinical trials. Based on our previous quantitative structure activity relationship (QSAR) and crystallographic studies, several novel pyridine-containing fosmidomycin derivatives were designed, synthesized and found to be highly potent inhibitors of P. falciparum DXR (PfDXR) having Ki values of 1.9 - 13 nM, with the best one being ~11x more active than fosmidomycin. These compounds also potently block the proliferation of multi-drug resistant P. falciparum with EC50 values as low as 170 nM. A 2.3 A crystal structure of PfDXR in complex with one of the inhibitors is reported, showing the flexible loop of the protein undergoes conformational changes upon ligand binding and a hydrogen bond and favorable hydrophobic interactions between the pyridine group and PfDXR account for the enhanced activity. | ||
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| - | Antimalarial and Structural Studies of Pyridine-containing Inhibitors of 1-Deoxyxylulose-5-phosphate Reductoisomerase.,Xue J, Diao J, Cai G, Deng L, Zheng B, Yao Y, Song Y ACS Med Chem Lett. 2013 Feb 14;4(2):278-282. PMID:23795240<ref>PMID:23795240</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4gae" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[DXP reductoisomerase|DXP reductoisomerase]] | + | *[[DXP reductoisomerase 3D Structures|DXP reductoisomerase 3D Structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Crystal structure of plasmodium dxr in complex with a pyridine-containing inhibitor
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Categories: Large Structures | Plasmodium falciparum HB3 | Cai G | Deng L | Diao J | Song Y | Xue J
