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| | <StructureSection load='4y6r' size='340' side='right'caption='[[4y6r]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='4y6r' size='340' side='right'caption='[[4y6r]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4y6r]] 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=4Y6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y6R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4y6r]] 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=4Y6R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y6R FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=RF7:{(2R)-4-[HYDROXY(METHYL)AMINO]-4-OXO-2-PHENYLBUTYL}PHOSPHONIC+ACID'>RF7</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=RF7:{(2R)-4-[HYDROXY(METHYL)AMINO]-4-OXO-2-PHENYLBUTYL}PHOSPHONIC+ACID'>RF7</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4y67|4y67]], [[4y6p|4y6p]]</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=4y6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y6r OCA], [https://pdbe.org/4y6r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y6r RCSB], [https://www.ebi.ac.uk/pdbsum/4y6r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y6r ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DXR, PF14_0641 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=4y6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y6r OCA], [http://pdbe.org/4y6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y6r RCSB], [http://www.ebi.ac.uk/pdbsum/4y6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y6r ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DXR_PLAF7 DXR_PLAF7]] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP). | + | [https://www.uniprot.org/uniprot/DXR_PLAF7 DXR_PLAF7] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==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: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plaf7]] | + | [[Category: Plasmodium falciparum 3D7]] |
| - | [[Category: Bergfors, T]] | + | [[Category: Bergfors T]] |
| - | [[Category: Jones, T A]] | + | [[Category: Jones TA]] |
| - | [[Category: Mowbray, S L]] | + | [[Category: Mowbray SL]] |
| - | [[Category: Sooriyaarachchi, S]] | + | [[Category: Sooriyaarachchi S]] |
| - | [[Category: Enzyme-inhibitor complex]]
| + | |
| - | [[Category: Isoprenoid biosynthesis]]
| + | |
| - | [[Category: Mep pathway]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
DXR_PLAF7 Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).
Publication Abstract from PubMed
Blocking the 2-C-methyl-d-erythrithol-4-phosphate (MEP) pathway for isoprenoid biosynthesis offers interesting prospects for inhibiting Plasmodium or Mycobacterium spp. growth. Fosmidomycin (1) and its homologue FR900098 (2) potently inhibit 1-deoxy-d-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in this pathway. Here we introduced aryl or aralkyl substituents at the beta-position of the hydroxamate analogue of 2. While direct addition of a beta-aryl moiety resulted in poor inhibition, longer linkers between the carbon backbone and the phenyl ring were generally associated with better binding to the enzymes. X-ray structures of the parasite Dxr-inhibitor complexes show that the "longer" compounds generate a substantially different flap structure, in which a key tryptophan residue is displaced, and the aromatic group of the ligand lies between the tryptophan and the hydroxamate's methyl group. Although the most promising new Dxr inhibitors lack activity against Escherichia coli and Mycobacterium smegmatis, they proved to be highly potent inhibitors of Plasmodium falciparum in vitro growth.
Synthesis and Bioactivity of beta-Substituted Fosmidomycin Analogues Targeting 1-Deoxy-d-xylulose-5-phosphate Reductoisomerase.,Chofor R, Sooriyaarachchi S, Risseeuw MD, Bergfors T, Pouyez J, Johny C, Haymond A, Everaert A, Dowd CS, Maes L, Coenye T, Alex A, Couch RD, Jones TA, Wouters J, Mowbray SL, Van Calenbergh S J Med Chem. 2015 Mar 31. PMID:25781377[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chofor R, Sooriyaarachchi S, Risseeuw MD, Bergfors T, Pouyez J, Johny C, Haymond A, Everaert A, Dowd CS, Maes L, Coenye T, Alex A, Couch RD, Jones TA, Wouters J, Mowbray SL, Van Calenbergh S. Synthesis and Bioactivity of beta-Substituted Fosmidomycin Analogues Targeting 1-Deoxy-d-xylulose-5-phosphate Reductoisomerase. J Med Chem. 2015 Mar 31. PMID:25781377 doi:http://dx.doi.org/10.1021/jm5014264
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