3ras: Difference between revisions
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== Structural highlights == | == 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> | <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>< | </td></tr><tr id='ligand'><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></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2jcz|2jcz]], [[2jcv|2jcv]]</td></tr> | <tr id='related'><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 id='gene'><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 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><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> | <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=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> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/DXR_MYCTU DXR_MYCTU]] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP) (By similarity). | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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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> | 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> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
== References == | == References == | ||
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[[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]] | [[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]] | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Deng, L | [[Category: Deng, L]] | ||
[[Category: Diao, J | [[Category: Diao, J]] | ||
[[Category: Prasad, B V.V | [[Category: Prasad, B V.V]] | ||
[[Category: Song, Y | [[Category: Song, Y]] | ||
[[Category: 1-deoxy-d-xylulose 5-phosphate reductoisomerase]] | [[Category: 1-deoxy-d-xylulose 5-phosphate reductoisomerase]] | ||
[[Category: Doxp/mep pathway]] | [[Category: Doxp/mep pathway]] | ||
Revision as of 02:59, 25 December 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
Function[DXR_MYCTU] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP) (By similarity). Publication Abstract from PubMed1-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
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