2c82: Difference between revisions
New page: left|200px<br /> <applet load="2c82" size="450" color="white" frame="true" align="right" spinBox="true" caption="2c82, resolution 1.90Å" /> '''X-RAY STRUCTURE OF ... |
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== | ==X-Ray Structure Of 1-Deoxy-D-xylulose 5-phosphate Reductoisomerase, DXR, Rv2870c, From Mycobacterium tuberculosis== | ||
1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzes the | <StructureSection load='2c82' size='340' side='right'caption='[[2c82]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2c82]] 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=2C82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C82 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=2c82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c82 OCA], [https://pdbe.org/2c82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c82 RCSB], [https://www.ebi.ac.uk/pdbsum/2c82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c82 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://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). | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c8/2c82_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2c82 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzes the NADPH-dependent rearrangement and reduction of 1-deoxy-D-xylulose 5-phosphate to form 2-C-methyl-D-erythritol 4-phosphate, as the second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway found in many bacteria and plants. The end product, isopentenyl diphosphate, is the precursor of various isoprenoids vital to all living organisms. The pathway is not found in humans; the mevalonate pathway is instead used for the formation of isopentenyl diphosphate. This difference, combined with its essentiality, makes the reductoisomerase an excellent drug target in a number of pathogenic organisms. The structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase from Mycobacterium tuberculosis (Rv2870c) was solved by molecular replacement and refined to a resolution of 1.9 A. The enzyme exhibited an estimated kcat of 5.3 s-1 and Km and kcat/Km values of 7.2 microM and 7.4x10(5) M-1 s-1 for NADPH and 340 microM and 1.6x10(4) M-1 s-1 for 1-deoxy-D-xylulose 5-phosphate. In the structure, a sulfate is bound at the expected site of the phosphate moiety of the sugar substrate. The M. tuberculosis enzyme displays a similar fold to the previously published structures from Escherichia coli and Zymomonas mobilis. Comparisons offer suggestions for the design of specific drugs. Furthermore, the new structure represents an intermediate conformation between the open apo form and the closed holo form observed previously, giving insights into the conformational changes associated with catalysis. | |||
The 1.9 A resolution structure of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a potential drug target.,Henriksson LM, Bjorkelid C, Mowbray SL, Unge T Acta Crystallogr D Biol Crystallogr. 2006 Jul;62(Pt 7):807-13. Epub 2006, Jun 20. PMID:16790937<ref>PMID:16790937</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2c82" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DXP reductoisomerase 3D Structures|DXP reductoisomerase 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis H37Rv]] | |||
[[Category: Bjorkelid C]] | |||
[[Category: Henriksson LM]] | |||
[[Category: Mowbray SL]] | |||
[[Category: Unge T]] | |||
Latest revision as of 17:08, 13 December 2023
X-Ray Structure Of 1-Deoxy-D-xylulose 5-phosphate Reductoisomerase, DXR, Rv2870c, From Mycobacterium tuberculosisX-Ray Structure Of 1-Deoxy-D-xylulose 5-phosphate Reductoisomerase, DXR, Rv2870c, From Mycobacterium tuberculosis
Structural highlights
FunctionDXR_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). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzes the NADPH-dependent rearrangement and reduction of 1-deoxy-D-xylulose 5-phosphate to form 2-C-methyl-D-erythritol 4-phosphate, as the second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway found in many bacteria and plants. The end product, isopentenyl diphosphate, is the precursor of various isoprenoids vital to all living organisms. The pathway is not found in humans; the mevalonate pathway is instead used for the formation of isopentenyl diphosphate. This difference, combined with its essentiality, makes the reductoisomerase an excellent drug target in a number of pathogenic organisms. The structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase from Mycobacterium tuberculosis (Rv2870c) was solved by molecular replacement and refined to a resolution of 1.9 A. The enzyme exhibited an estimated kcat of 5.3 s-1 and Km and kcat/Km values of 7.2 microM and 7.4x10(5) M-1 s-1 for NADPH and 340 microM and 1.6x10(4) M-1 s-1 for 1-deoxy-D-xylulose 5-phosphate. In the structure, a sulfate is bound at the expected site of the phosphate moiety of the sugar substrate. The M. tuberculosis enzyme displays a similar fold to the previously published structures from Escherichia coli and Zymomonas mobilis. Comparisons offer suggestions for the design of specific drugs. Furthermore, the new structure represents an intermediate conformation between the open apo form and the closed holo form observed previously, giving insights into the conformational changes associated with catalysis. The 1.9 A resolution structure of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a potential drug target.,Henriksson LM, Bjorkelid C, Mowbray SL, Unge T Acta Crystallogr D Biol Crystallogr. 2006 Jul;62(Pt 7):807-13. Epub 2006, Jun 20. PMID:16790937[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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