2y1e: Difference between revisions
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<StructureSection load='2y1e' size='340' side='right'caption='[[2y1e]], [[Resolution|resolution]] 1.65Å' scene=''> | <StructureSection load='2y1e' size='340' side='right'caption='[[2y1e]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2y1e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2y1e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y1E FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> | ||
<tr id=' | <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=SO4:SULFATE+ION'>SO4</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=2y1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y1e OCA], [https://pdbe.org/2y1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y1e RCSB], [https://www.ebi.ac.uk/pdbsum/2y1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y1e 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=2y1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y1e OCA], [https://pdbe.org/2y1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y1e RCSB], [https://www.ebi.ac.uk/pdbsum/2y1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y1e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<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: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Bergfors | [[Category: Bergfors T]] | ||
[[Category: Bjorkelid | [[Category: Bjorkelid C]] | ||
[[Category: Henriksson | [[Category: Henriksson LM]] | ||
[[Category: Jones | [[Category: Jones TA]] | ||
[[Category: Larsson | [[Category: Larsson AMS]] | ||
[[Category: Mowbray | [[Category: Mowbray SL]] | ||
[[Category: Unge | [[Category: Unge T]] | ||
Latest revision as of 13:43, 20 December 2023
X-ray structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, DXR, Rv2870c, from Mycobacterium tuberculosis, in complex with manganese.X-ray structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, DXR, Rv2870c, from Mycobacterium tuberculosis, in complex with manganese.
Structural highlights
Publication Abstract from PubMedThe natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR) but it lacks antibacterial activity, probably because of poor uptake. alpha-Aryl substituted fosmidomycin analogues have more favorable physicochemical properties, and are also more active in inhibiting malaria parasite growth. We have solved crystal structures of MtDXR in complex with 3,4-dichlorophenyl substituted fosmidomycin analogues; these show important differences compared to our previously described forsmidomycin-DXR complex. Our best inhibitor has an IC50 = 0.15 muM on MtDXR but still lacked activity in a mycobacterial growth assay (MICs > 32 mug/ml). The combined results, however, provide insights into how DXR accommodates the new inhibitors and serve as an excellent starting point for the design of other novel and more potent inhibitors, particularly against pathogens where uptake is less of a problem, such as the malaria parasite. Design, Synthesis and X-ray Crystallographic Studies of alpha-Aryl Substituted Fosmidomycin Analogues as Inhibitors of Mycobacterium tuberculosis 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase.,Andaloussi M, Henriksson LM, Wieckowska A, Lindh M, Bjorkelid C, Larsson AM, Suresh S, Iyer H, Srinivasa BR, Bergfors T, Unge T, Mowbray SL, Larhed ML, Jones AT, Karlen AB J Med Chem. 2011 Jun 16. PMID:21678907[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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