|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of the ternary complex of an isomerase== | | ==Crystal structure of the ternary complex of an isomerase== |
| - | <StructureSection load='3au8' size='340' side='right' caption='[[3au8]], [[Resolution|resolution]] 1.86Å' scene=''> | + | <StructureSection load='3au8' size='340' side='right'caption='[[3au8]], [[Resolution|resolution]] 1.86Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3au8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AU8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3au8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AU8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 1.86Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3au9|3au9]], [[3aua|3aua]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dxr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</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=3au8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3au8 OCA], [https://pdbe.org/3au8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3au8 RCSB], [https://www.ebi.ac.uk/pdbsum/3au8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3au8 ProSAT]</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=3au8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3au8 OCA], [http://pdbe.org/3au8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3au8 RCSB], [http://www.ebi.ac.uk/pdbsum/3au8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3au8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 21: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[DXP reductoisomerase|DXP reductoisomerase]] | + | *[[DXP reductoisomerase 3D Structures|DXP reductoisomerase 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Plafa]] | + | [[Category: Large Structures]] |
| - | [[Category: Kitade, Y]] | + | [[Category: Plasmodium falciparum]] |
| - | [[Category: Kusakabe, Y]] | + | [[Category: Kitade Y]] |
| - | [[Category: Nakamura, K T]] | + | [[Category: Kusakabe Y]] |
| - | [[Category: Nakanishi, M]] | + | [[Category: Nakamura KT]] |
| - | [[Category: Tanaka, N]] | + | [[Category: Nakanishi M]] |
| - | [[Category: Umeda, T]] | + | [[Category: Tanaka N]] |
| - | [[Category: Isomerase]]
| + | [[Category: Umeda T]] |
| - | [[Category: Nadph binding]]
| + | |
| Structural highlights
Function
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).[1]
Publication Abstract from PubMed
The human malaria parasite Plasmodium falciparum is responsible for the deaths of more than a million people each year. Fosmidomycin has been proven to be efficient in the treatment of P. falciparum malaria by inhibiting 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an enzyme of the non-mevalonate pathway, which is absent in humans. However, the structural details of DXR inhibition by fosmidomycin in P. falciparum are unknown. Here, we report the crystal structures of fosmidomycin-bound complete quaternary complexes of PfDXR. Our study revealed that (i) an intrinsic flexibility of the PfDXR molecule accounts for an induced-fit movement to accommodate the bound inhibitor in the active site and (ii) a cis arrangement of the oxygen atoms of the hydroxamate group of the bound inhibitor is essential for tight binding of the inhibitor to the active site metal. We expect the present structures to be useful guides for the design of more effective antimalarial compounds.
Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum.,Umeda T, Tanaka N, Kusakabe Y, Nakanishi M, Kitade Y, Nakamura KT Sci Rep. 2011;1:9. doi: 10.1038/srep00009. Epub 2011 Jun 14. PMID:22355528[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Turbachova I, Eberl M, Zeidler J, Lichtenthaler HK, Soldati D, Beck E. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science. 1999 Sep 3;285(5433):1573-6. PMID:10477522
- ↑ Umeda T, Tanaka N, Kusakabe Y, Nakanishi M, Kitade Y, Nakamura KT. Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum. Sci Rep. 2011;1:9. doi: 10.1038/srep00009. Epub 2011 Jun 14. PMID:22355528 doi:10.1038/srep00009
|
