2y1d: Difference between revisions

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-[[Image:2y1d.png|left|200px]]
+==X-RAY STRUCTURE OF 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE, DXR, RV2870C, FROM MYCOBACTERIUM TUBERCULOSIS, IN COMPLEX WITH A 3,4-DICHLOROPHENYL-SUBSTITUTED FOSMIDOMYCIN ANALOGUE AND MANGANESE.==
+<StructureSection load='2y1d' size='340' side='right' caption='[[2y1d]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2y1d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y1D OCA]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=34F:(1S)-1-(3,4-DICHLOROPHENYL)-3-[FORMYL(HYDROXY)AMINO]PROPYL}PHOSPHONIC+ACID'>34F</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2y1c|2y1c]], [[2y1e|2y1e]], [[2y1f|2y1f]], [[2y1g|2y1g]]</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2y1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y1d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y1d RCSB], [http://www.ebi.ac.uk/pdbsum/2y1d PDBsum]</span></td></tr>
+<table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The 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 &gt; 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<ref>PMID:21678907</ref>
-The line below this paragraph, containing "STRUCTURE_2y1d", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
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-{{STRUCTURE_2y1d|  PDB=2y1d  |  SCENE=  }}
-===X-RAY STRUCTURE OF 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE, DXR, RV2870C, FROM MYCOBACTERIUM TUBERCULOSIS, IN COMPLEX WITH A 3,4-DICHLOROPHENYL-SUBSTITUTED FOSMIDOMYCIN ANALOGUE AND MANGANESE.===
+From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+</div>
+== References ==
-<!--
+<references/>
-The line below this paragraph, {{ABSTRACT_PUBMED_21678907}}, adds the Publication Abstract to the page
+__TOC__
-(as it appears on PubMed at http://www.pubmed.gov), where 21678907 is the PubMed ID number.
+</StructureSection>
--->
-{{ABSTRACT_PUBMED_21678907}}
-==About this Structure==
-[[2y1d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y1D OCA].
-==Reference==
-<ref group="xtra">PMID:021678907</ref><ref group="xtra">PMID:016790937</ref><ref group="xtra">PMID:017491006</ref><references group="xtra"/>
 [[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]]
 [[Category: Mycobacterium tuberculosis]]