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[[Image:3ras.png|left|200px]]
==Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) complexed with a lipophilic phosphonate inhibitor==
<StructureSection load='3ras' size='340' side='right' caption='[[3ras]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ras]] 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=3RAS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RAS FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DCV:[(1R)-3-[ACETYL(HYDROXY)AMINO]-1-(3,4-DICHLOROPHENYL)PROPYL]PHOSPHONIC+ACID'>DCV</scene>, <scene name='pdbligand=FM5:3-(N-HYDROXYACETAMIDO)-1-(3,4-DICHLOROPHENYL)PROPYLPHOSPHONIC+ACID'>FM5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2jcz|2jcz]], [[2jcv|2jcv]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dxr, Rv2870c, MT2938, MTCY274.01c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr>
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ras FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ras OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ras RCSB], [http://www.ebi.ac.uk/pdbsum/3ras PDBsum]</span></td></tr>
<table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including anti-tuberculosis) and antimalaria drugs. 41 lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a Ki of 420 nM. Structure activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been well performed, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.


{{STRUCTURE_3ras|  PDB=3ras  |  SCENE=  }}
Inhibition of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase by Lipophilic Phosphonates: SAR, QSAR and Crystallographic Studies.,Deng L, Diao J, Chen P, Pujari V, Yao Y, Cheng G, Crick DC, Prasad BV, Song Y J Med Chem. 2011 May 11. PMID:21561155<ref>PMID:21561155</ref>


===Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) complexed with a lipophilic phosphonate inhibitor===
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_21561155}}
== References ==
 
<references/>
==About this Structure==
__TOC__
[[3ras]] 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=3RAS OCA].
</StructureSection>
 
==Reference==
<ref group="xtra">PMID:021561155</ref><references group="xtra"/>
[[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]]
[[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]

Revision as of 07:46, 5 June 2014

Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) complexed with a lipophilic phosphonate inhibitorCrystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) complexed with a lipophilic phosphonate inhibitor

Structural highlights

3ras is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , ,
Related:2jcz, 2jcv
Gene:dxr, Rv2870c, MT2938, MTCY274.01c (Mycobacterium tuberculosis)
Activity:1-deoxy-D-xylulose-5-phosphate reductoisomerase, with EC number 1.1.1.267
Resources:FirstGlance, OCA, RCSB, PDBsum

Publication Abstract from PubMed

1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including anti-tuberculosis) and antimalaria drugs. 41 lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a Ki of 420 nM. Structure activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been well performed, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.

Inhibition of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase by Lipophilic Phosphonates: SAR, QSAR and Crystallographic Studies.,Deng L, Diao J, Chen P, Pujari V, Yao Y, Cheng G, Crick DC, Prasad BV, Song Y J Med Chem. 2011 May 11. PMID:21561155[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Deng L, Diao J, Chen P, Pujari V, Yao Y, Cheng G, Crick DC, Prasad BV, Song Y. Inhibition of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase by Lipophilic Phosphonates: SAR, QSAR and Crystallographic Studies. J Med Chem. 2011 May 11. PMID:21561155 doi:10.1021/jm200363d

3ras, resolution 2.55Å

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