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4feh

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==Mycobacterium tuberculosis DprE1 - hexagonal crystal form==
==Mycobacterium tuberculosis DprE1 - hexagonal crystal form==
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<StructureSection load='4feh' size='340' side='right' caption='[[4feh]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
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<StructureSection load='4feh' size='340' side='right'caption='[[4feh]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4feh]] is a 1 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=4FEH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FEH FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4feh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FEH FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.035&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fdp|4fdp]], [[4fdn|4fdn]], [[4fdo|4fdo]], [[4ff6|4ff6]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dprE1, MT3898, Rv3790 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4feh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4feh OCA], [https://pdbe.org/4feh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4feh RCSB], [https://www.ebi.ac.uk/pdbsum/4feh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4feh ProSAT]</span></td></tr>
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<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=4feh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4feh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4feh RCSB], [http://www.ebi.ac.uk/pdbsum/4feh PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/DPRE1_MYCTU DPRE1_MYCTU] Involved in the epimerization of decaprenylphosphoryl ribose (DPR) to decaprenylphosphoryl arabinose (DPA) a precursor for arabinan synthesis in mycobacterial cell wall biosynthesis. Probably catalyzes the oxidation at C-2 of decaprenylphosphoryl ribose (DPR) to yield decaprenylphosphoryl 2-keto-ribose (DPX).<ref>PMID:16291675</ref>
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Resistance against currently used antitubercular therapeutics increasingly undermines efforts to contain the worldwide tuberculosis (TB) epidemic. Recently, benzothiazinone (BTZ) inhibitors have shown nanomolar potency against both drug-susceptible and multidrug-resistant strains of the tubercle bacillus. However, their proposed mode of action is lacking structural evidence. We report here the crystal structure of the BTZ target, FAD-containing oxidoreductase Mycobacterium tuberculosis DprE1, which is essential for viability. Different crystal forms of ligand-free DprE1 reveal considerable levels of structural flexibility of two surface loops that seem to govern accessibility of the active site. Structures of complexes with the BTZ-derived nitroso derivative CT325 reveal the mode of inhibitor binding, which includes a covalent link to conserved Cys387, and reveal a trifluoromethyl group as a second key determinant of interaction with the enzyme. Surprisingly, we find that a noncovalent complex was formed between DprE1 and CT319, which is structurally identical to CT325 except for an inert nitro group replacing the reactive nitroso group. This demonstrates that binding of BTZ-class inhibitors to DprE1 is not strictly dependent on formation of the covalent link to Cys387. On the basis of the structural and activity data, we propose that the complex of DrpE1 bound to CT325 is a representative of the BTZ-target complex. These results mark a significant step forward in the characterization of a key TB drug target.
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Structural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors.,Batt SM, Jabeen T, Bhowruth V, Quill L, Lund PA, Eggeling L, Alderwick LJ, Futterer K, Besra GS Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11354-9. Epub 2012 Jun 25. PMID:22733761<ref>PMID:22733761</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
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[[Category: Batt, S M]]
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[[Category: Batt SM]]
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[[Category: Besra, G S]]
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[[Category: Besra GS]]
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[[Category: Futterer, K]]
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[[Category: Futterer K]]
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[[Category: Alpha+beta]]
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[[Category: Decaprenylphosphoryl-beta-d-ribose]]
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[[Category: Oxidoreductase]]
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Current revision

Mycobacterium tuberculosis DprE1 - hexagonal crystal form

PDB ID 4feh

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