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| | <StructureSection load='7pwb' size='340' side='right'caption='[[7pwb]], [[Resolution|resolution]] 1.87Å' scene=''> | | <StructureSection load='7pwb' size='340' side='right'caption='[[7pwb]], [[Resolution|resolution]] 1.87Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7pwb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PWB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7pwb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxiella_burnetii_RSA_493 Coxiella burnetii RSA 493]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PWB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=TYD:THYMIDINE-5-DIPHOSPHATE'>TYD</scene></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]] 1.87Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7pvi|7pvi]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=TYD:THYMIDINE-5-DIPHOSPHATE'>TYD</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dTDP-4-dehydrorhamnose_3,5-epimerase dTDP-4-dehydrorhamnose 3,5-epimerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.3.13 5.1.3.13] </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=7pwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pwb OCA], [https://pdbe.org/7pwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pwb RCSB], [https://www.ebi.ac.uk/pdbsum/7pwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pwb 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=7pwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pwb OCA], [https://pdbe.org/7pwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pwb RCSB], [https://www.ebi.ac.uk/pdbsum/7pwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pwb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/Q83AP3_COXBU Q83AP3_COXBU]] Catalyzes the epimerization of the C3' and C5'positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose.[ARBA:ARBA00001997][RuleBase:RU364069]
| + | [https://www.uniprot.org/uniprot/Q83AP3_COXBU Q83AP3_COXBU] Catalyzes the epimerization of the C3' and C5'positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose.[ARBA:ARBA00001997][RuleBase:RU364069] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Coxiella burnetii RSA 493]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: DTDP-4-dehydrorhamnose 3,5-epimerase]]
| + | [[Category: Cross AR]] |
| - | [[Category: Cross, A R]] | + | [[Category: Harmer NJ]] |
| - | [[Category: Harmer, N J]] | + | [[Category: Isupov MN]] |
| - | [[Category: Isupov, M N]] | + | |
| - | [[Category: Coxiella burnetii]]
| + | |
| - | [[Category: Enzyme kinetic]]
| + | |
| - | [[Category: Epimerase]]
| + | |
| - | [[Category: O-antigen]]
| + | |
| - | [[Category: Sugar binding protein]]
| + | |
| Structural highlights
Function
Q83AP3_COXBU Catalyzes the epimerization of the C3' and C5'positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose.[ARBA:ARBA00001997][RuleBase:RU364069]
Publication Abstract from PubMed
The sugars streptose and dihydrohydroxystreptose (DHHS) are unique to the bacteria Streptomyces griseus and Coxiella burnetii, respectively. Streptose forms the central moiety of the antibiotic streptomycin, whilst DHHS is found in the O-antigen of the zoonotic pathogen C. burnetii. Biosynthesis of these sugars has been proposed to follow a similar path to that of TDP-rhamnose, catalyzed by the enzymes RmlA, RmlB, RmlC, and RmlD, but the exact mechanism is unclear. Streptose and DHHS biosynthesis unusually requires a ring contraction step that could be performed by orthologues of RmlC or RmlD. Genome sequencing of S. griseus and C. burnetii has identified StrM and CBU1838 proteins as RmlC orthologues in these respective species. Here, we demonstrate that both enzymes can perform the RmlC 3,5 double epimerization activity necessary to support TDP-rhamnose biosynthesis in vivo. This is consistent with the ring contraction step being performed on a double epimerized substrate. We further demonstrate that proton exchange is faster at the 3-position than the 5-position, in contrast to a previously studied orthologue. We additionally solved the crystal structures of CBU1838 and StrM in complex with TDP, and show that they form an active site highly similar to those of the previously characterized enzymes RmlC, EvaD, and ChmJ. These results support the hypothesis that streptose and DHHS are biosynthesized using the TDP pathway and that an RmlD paralogue most likely performs ring contraction following double epimerization. This work will support the elucidation of the full pathways for biosynthesis of these unique sugars.
Spinning sugars in antigen biosynthesis: characterization of the Coxiella burnetii and Streptomyces griseus TDP-sugar epimerases.,Cross AR, Roy S, Vivoli Vega M, Rejzek M, Nepogodiev SA, Cliff M, Salmon D, Isupov MN, Field RA, Prior JL, Harmer NJ J Biol Chem. 2022 Apr 6:101903. doi: 10.1016/j.jbc.2022.101903. PMID:35398092[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cross AR, Roy S, Vivoli Vega M, Rejzek M, Nepogodiev SA, Cliff M, Salmon D, Isupov MN, Field RA, Prior JL, Harmer NJ. Spinning sugars in antigen biosynthesis: characterization of the Coxiella burnetii and Streptomyces griseus TDP-sugar epimerases. J Biol Chem. 2022 Apr 6:101903. doi: 10.1016/j.jbc.2022.101903. PMID:35398092 doi:http://dx.doi.org/10.1016/j.jbc.2022.101903
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