5jo0: Difference between revisions
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<StructureSection load='5jo0' size='340' side='right'caption='[[5jo0]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='5jo0' size='340' side='right'caption='[[5jo0]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5jo0]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5jo0]] 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=5JO0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JO0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6LR:MORPHOLINE'>6LR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L56:[(2R)-2-{2-[HYDROXY(METHYL)AMINO]-2-OXOETHYL}-5-(3-METHYLPHENYL)PENTYL]PHOSPHONIC+ACID'>L56</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6LR:MORPHOLINE'>6LR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L56:[(2R)-2-{2-[HYDROXY(METHYL)AMINO]-2-OXOETHYL}-5-(3-METHYLPHENYL)PENTYL]PHOSPHONIC+ACID'>L56</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=5jo0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jo0 OCA], [https://pdbe.org/5jo0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jo0 RCSB], [https://www.ebi.ac.uk/pdbsum/5jo0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jo0 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Plasmodium falciparum 3D7]] | ||
[[Category: Bergfors | [[Category: Bergfors T]] | ||
[[Category: Jones | [[Category: Jones TA]] | ||
[[Category: Mowbray | [[Category: Mowbray SL]] | ||
[[Category: Sooriyaarachchi | [[Category: Sooriyaarachchi S]] | ||
Latest revision as of 22:00, 20 September 2023
Structure of Plasmodium falciparum DXR in complex with a beta-substituted fosmidomycin analogue, LC56 and manganeseStructure of Plasmodium falciparum DXR in complex with a beta-substituted fosmidomycin analogue, LC56 and manganese
Structural highlights
FunctionDXR_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 PubMedBlocking the 2-C-methyl-d-erythrithol-4-phosphate pathway for isoprenoid biosynthesis offers new ways to inhibit the growth of Plasmodium spp. Fosmidomycin [(3-(N-hydroxyformamido)propyl)phosphonic acid, 1] and its acetyl homologue FR-900098 [(3-(N-hydroxyacetamido)propyl)phosphonic acid, 2] potently inhibit 1-deoxy-d-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in this biosynthetic pathway. Arylpropyl substituents were introduced at the beta-position of the hydroxamate analogue of 2 to study changes in lipophilicity, as well as electronic and steric properties. The potency of several new compounds on the P. falciparum enzyme approaches that of 1 and 2. Activities against the enzyme and parasite correlate well, supporting the mode of action. Seven X-ray structures show that all of the new arylpropyl substituents displace a key tryptophan residue of the active-site flap, which had made favorable interactions with 1 and 2. Plasticity of the flap allows substituents to be accommodated in many ways; in most cases, the flap is largely disordered. Compounds can be separated into two classes based on whether the substituent on the aromatic ring is at the meta or para position. Generally, meta-substituted compounds are better inhibitors, and in both classes, smaller size is linked to better potency. Targeting an Aromatic Hotspot in Plasmodium falciparum 1-Deoxy-d-xylulose-5-phosphate Reductoisomerase with beta-Arylpropyl Analogues of Fosmidomycin.,Sooriyaarachchi S, Chofor R, Risseeuw MD, Bergfors T, Pouyez J, Dowd CS, Maes L, Wouters J, Jones TA, Van Calenbergh S, Mowbray SL ChemMedChem. 2016 Aug 3. doi: 10.1002/cmdc.201600249. PMID:27487410[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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