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| | ==Structure of Plasmodium IspC in complex with a beta-thia-isostere derivative of Fosmidomycin== | | ==Structure of Plasmodium IspC in complex with a beta-thia-isostere derivative of Fosmidomycin== |
| - | <StructureSection load='4kp7' size='340' side='right' caption='[[4kp7]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4kp7' size='340' side='right'caption='[[4kp7]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kp7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafx Plafx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KP7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KP7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kp7]] 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=4KP7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KP7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1UQ:[(S)-({2-[HYDROXY(METHYL)AMINO]-2-OXOETHYL}SULFANYL)(PHENYL)METHYL]PHOSPHONIC+ACID'>1UQ</scene>, <scene name='pdbligand=MN3:MANGANESE+(III)+ION'>MN3</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1UQ:[(S)-({2-[HYDROXY(METHYL)AMINO]-2-OXOETHYL}SULFANYL)(PHENYL)METHYL]PHOSPHONIC+ACID'>1UQ</scene>, <scene name='pdbligand=MN3:MANGANESE+(III)+ION'>MN3</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3au8|3au8]], [[3au9|3au9]]</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=4kp7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kp7 OCA], [https://pdbe.org/4kp7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kp7 RCSB], [https://www.ebi.ac.uk/pdbsum/4kp7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kp7 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">codon optimized form, DXR, synthetic ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=137071 PLAFX])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/1-deoxy-D-xylulose-5-phosphate_reductoisomerase 1-deoxy-D-xylulose-5-phosphate reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.267 1.1.1.267] </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=4kp7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kp7 OCA], [http://pdbe.org/4kp7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kp7 RCSB], [http://www.ebi.ac.uk/pdbsum/4kp7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kp7 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 == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Plafx]] | + | [[Category: Plasmodium falciparum HB3]] |
| - | [[Category: Bacher, A]] | + | [[Category: Bacher A]] |
| - | [[Category: Groll, M]] | + | [[Category: Groll M]] |
| - | [[Category: Kunfermann, A]] | + | [[Category: Kunfermann A]] |
| - | [[Category: Apicoplast]]
| + | |
| - | [[Category: Drug optimization]]
| + | |
| - | [[Category: Dxp pathway]]
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| - | [[Category: Malaria]]
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| - | [[Category: Nadph binding]]
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| - | [[Category: Non-covalent inhibition]]
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| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| - | [[Category: Reductoisomerase]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: Tuberculosis]]
| + | |
| 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 emergence and spread of multidrug-resistant pathogens is widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the synthesis and properties of "reverse" thia-analogs of fosmidomycin, which inhibit the first committed enzyme of a metabolic pathway that is essential for the causative agents of tuberculosis and malaria but is absent in the human host. Notably, IspC displays a high level of enantioselectivity for an alpha-susbtituted fosmidomycin derivative.
IspC as target for antiinfective drug discovery: Synthesis, enantiomeric separation and structural biology of fosmidomycin thia-isosters.,Kunfermann A, Lienau C, Illarionov B, Held J, Grawert T, Behrendt CT, Werner P, Hahn S, Eisenreich W, Riederer U, Mordmuller B, Bacher A, Fischer M, Groll M, Kurz T J Med Chem. 2013 Sep 13. PMID:24032981[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
- ↑ Kunfermann A, Lienau C, Illarionov B, Held J, Grawert T, Behrendt CT, Werner P, Hahn S, Eisenreich W, Riederer U, Mordmuller B, Bacher A, Fischer M, Groll M, Kurz T. IspC as target for antiinfective drug discovery: Synthesis, enantiomeric separation and structural biology of fosmidomycin thia-isosters. J Med Chem. 2013 Sep 13. PMID:24032981 doi:10.1021/jm4012559
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