4a03: Difference between revisions
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<StructureSection load='4a03' size='340' side='right'caption='[[4a03]], [[Resolution|resolution]] 1.65Å' scene=''> | <StructureSection load='4a03' size='340' side='right'caption='[[4a03]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4a03]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4a03]] 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=4A03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A03 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F98:3-[ETHANOYL(HYDROXY)AMINO]PROPYLPHOSPHONIC+ACID'>F98</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene | </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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F98:3-[ETHANOYL(HYDROXY)AMINO]PROPYLPHOSPHONIC+ACID'>F98</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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=4a03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a03 OCA], [https://pdbe.org/4a03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a03 RCSB], [https://www.ebi.ac.uk/pdbsum/4a03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a03 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=4a03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a03 OCA], [https://pdbe.org/4a03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a03 RCSB], [https://www.ebi.ac.uk/pdbsum/4a03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a03 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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). | |||
<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: Jones | [[Category: Jones TA]] | ||
Latest revision as of 14:17, 20 December 2023
Crystal Structure of Mycobacterium tuberculosis DXR in complex with the antibiotic FR900098 and cofactor NADPHCrystal Structure of Mycobacterium tuberculosis DXR in complex with the antibiotic FR900098 and cofactor NADPH
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). Publication Abstract from PubMedA number of pathogens, including the causative agents of tuberculosis and malaria, synthesize the essential isoprenoid precursor isopentenyl diphosphate via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway rather than the classical mevalonate pathway that is found in humans. As part of a structure-based drug-discovery program against tuberculosis, DXR, the enzyme that carries out the second step in the MEP pathway, has been investigated. This enzyme is the target for the antibiotic fosmidomycin and its active acetyl derivative FR-900098. The structure of DXR from Mycobacterium tuberculosis in complex with FR-900098, manganese and the NADPH cofactor has been solved and refined. This is a new crystal form that diffracts to a higher resolution than any other DXR complex reported to date. Comparisons with other ternary complexes show that the conformation is that of the enzyme in an active state: the active-site flap is well defined and the cofactor-binding domain has a conformation that brings the NADPH into the active site in a manner suitable for catalysis. The substrate-binding site is highly conserved in a number of pathogens that use this pathway, so any new inhibitor that is designed for the M. tuberculosis enzyme is likely to exhibit broad-spectrum activity. Structural studies on Mycobacterium tuberculosis DXR in complex with the antibiotic FR-900098.,Bjorkelid C, Bergfors T, Unge T, Mowbray SL, Jones TA Acta Crystallogr D Biol Crystallogr. 2012 Feb;68(Pt 2):134-43. Epub 2012 Jan 6. PMID:22281742[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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