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| | ==Mycobacterium smegmatis DprE1 - hexagonal crystal form== | | ==Mycobacterium smegmatis DprE1 - hexagonal crystal form== |
| - | <StructureSection load='4g3t' size='340' side='right' caption='[[4g3t]], [[Resolution|resolution]] 2.35Å' scene=''> | + | <StructureSection load='4g3t' size='340' side='right'caption='[[4g3t]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g3t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_smegmatis Mycobacterium smegmatis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G3T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G3T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4g3t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis Mycolicibacterium smegmatis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G3T FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g3u|4g3u]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.346Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MSMEG_6382 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1772 Mycobacterium smegmatis])</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=4g3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g3t OCA], [https://pdbe.org/4g3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g3t RCSB], [https://www.ebi.ac.uk/pdbsum/4g3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g3t ProSAT]</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=4g3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g3t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g3t RCSB], [http://www.ebi.ac.uk/pdbsum/4g3t PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/DPRE1_MYCS2 DPRE1_MYCS2] Component of the DprE1-DprE2 complex that catalyzes the 2-step epimerization of decaprenyl-phospho-ribose (DPR) to decaprenyl-phospho-arabinose (DPA), a key precursor that serves as the arabinose donor required for the synthesis of cell-wall arabinans (PubMed:22188377). DprE1 catalyzes the first step of epimerization, namely FAD-dependent oxidation of the C2' hydroxyl of DPR to yield the keto intermediate decaprenyl-phospho-2'-keto-D-arabinose (DPX) (PubMed:22188377). The intermediate DPX is then transferred to DprE2 subunit of the epimerase complex, most probably through a 'substrate channel' at the interface of DprE1-DprE2 complex (By similarity). Can also use farnesyl-phosphoryl-beta-D-ribofuranose (FPR) as substrate in vitro (PubMed:22188377, PubMed:22956199). Appears to be essential for the growth of M.smegmatis (PubMed:21346818).[UniProtKB:P9WJF1]<ref>PMID:21346818</ref> <ref>PMID:22188377</ref> <ref>PMID:22956199</ref> |
| - | Decaprenylphosphoryl-beta-D-ribose 2'-epimerase (DprE1) is an essential enzyme in the biosynthesis of cell wall components and a target for development of anti-tuberculosis drugs. We determined the crystal structure of a truncated form of DprE1 from Mycobacterium smegmatis in two crystal forms to up to 2.35 A resolution. The structure extends from residue 75 to the C-terminus and shares homology with FAD-dependent oxidoreductases of the vanillyl-alcohol oxidase family including the DprE1 homologue from M. tuberculosis. The M. smegmatis DprE1 structure reported here provides further insights into the active site geometry of this tuberculosis drug target.
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| - | Crystal structure of decaprenylphosphoryl-beta- D-ribose 2'-epimerase from Mycobacterium smegmatis.,Li H, Jogl G Proteins. 2013 Mar;81(3):538-43. doi: 10.1002/prot.24220. Epub 2012 Dec 24. PMID:23184707<ref>PMID:23184707</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Mycobacterium smegmatis]] | + | [[Category: Large Structures]] |
| - | [[Category: Jogl, G]] | + | [[Category: Mycolicibacterium smegmatis]] |
| - | [[Category: Li, H]] | + | [[Category: Jogl G]] |
| - | [[Category: Oxidoreductase]] | + | [[Category: Li H]] |
| - | [[Category: Vao superfamily]]
| + | |
| Structural highlights
Function
DPRE1_MYCS2 Component of the DprE1-DprE2 complex that catalyzes the 2-step epimerization of decaprenyl-phospho-ribose (DPR) to decaprenyl-phospho-arabinose (DPA), a key precursor that serves as the arabinose donor required for the synthesis of cell-wall arabinans (PubMed:22188377). DprE1 catalyzes the first step of epimerization, namely FAD-dependent oxidation of the C2' hydroxyl of DPR to yield the keto intermediate decaprenyl-phospho-2'-keto-D-arabinose (DPX) (PubMed:22188377). The intermediate DPX is then transferred to DprE2 subunit of the epimerase complex, most probably through a 'substrate channel' at the interface of DprE1-DprE2 complex (By similarity). Can also use farnesyl-phosphoryl-beta-D-ribofuranose (FPR) as substrate in vitro (PubMed:22188377, PubMed:22956199). Appears to be essential for the growth of M.smegmatis (PubMed:21346818).[UniProtKB:P9WJF1][1] [2] [3]
References
- ↑ Crellin PK, Brammananth R, Coppel RL. Decaprenylphosphoryl-beta-D-ribose 2'-epimerase, the target of benzothiazinones and dinitrobenzamides, is an essential enzyme in Mycobacterium smegmatis. PLoS One. 2011 Feb 8;6(2):e16869. doi: 10.1371/journal.pone.0016869. PMID:21346818 doi:http://dx.doi.org/10.1371/journal.pone.0016869
- ↑ Trefzer C, Skovierova H, Buroni S, Bobovska A, Nenci S, Molteni E, Pojer F, Pasca MR, Makarov V, Cole ST, Riccardi G, Mikusova K, Johnsson K. Benzothiazinones are suicide inhibitors of mycobacterial decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase DprE1. J Am Chem Soc. 2012 Jan 18;134(2):912-5. doi: 10.1021/ja211042r. Epub 2011 Dec, 21. PMID:22188377 doi:http://dx.doi.org/10.1021/ja211042r
- ↑ Neres J, Pojer F, Molteni E, Chiarelli LR, Dhar N, Boy-Rottger S, Buroni S, Fullam E, Degiacomi G, Lucarelli AP, Read RJ, Zanoni G, Edmondson DE, De Rossi E, Pasca MR, McKinney JD, Dyson PJ, Riccardi G, Mattevi A, Cole ST, Binda C. Structural Basis for Benzothiazinone-Mediated Killing of Mycobacterium tuberculosis. Sci Transl Med. 2012 Sep 5;4(150):150ra121. PMID:22956199 doi:http://dx.doi.org/10.1126/scitranslmed.3004395
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