|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6b5k' size='340' side='right'caption='[[6b5k]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='6b5k' size='340' side='right'caption='[[6b5k]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6b5k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B5K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6b5k]] 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=6B5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B5K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</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]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rmlA, rfbA, Rv0334 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</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'>[http://en.wikipedia.org/wiki/Glucose-1-phosphate_thymidylyltransferase Glucose-1-phosphate thymidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.24 2.7.7.24] </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=6b5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b5k OCA], [https://pdbe.org/6b5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b5k RCSB], [https://www.ebi.ac.uk/pdbsum/6b5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b5k 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=6b5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b5k OCA], [http://pdbe.org/6b5k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b5k RCSB], [http://www.ebi.ac.uk/pdbsum/6b5k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b5k ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/RMLA_MYCTU RMLA_MYCTU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glucose-1-phosphate thymidylyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Brown, H A]] | + | [[Category: Brown HA]] |
| - | [[Category: Holden, H A]] | + | [[Category: Holden HA]] |
| - | [[Category: Nucleotidyltransferase]]
| + | |
| - | [[Category: Substrate]]
| + | |
| - | [[Category: Sugar-modifying]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
RMLA_MYCTU
Publication Abstract from PubMed
Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, continues to be a major threat to populations worldwide. Whereas the disease is treatable, the drug regimen is arduous at best with the use of four antimicrobials over a six-month period. There is clearly a pressing need for the development of new therapeutics. One potential target for structure-based drug design is the enzyme RmlA, a glucose-1-phosphate thymidylyltransferase. This enzyme catalyzes the first step in the biosynthesis of l-rhamnose, which is a deoxysugar critical for the integrity of the bacterium's cell wall. Here, we report the X-ray structures of M. tuberculosis RmlA in complex with either dTTP or dTDP-glucose to 1.6 A and 1.85 A resolution, respectively. In the RmlA/dTTP complex, two magnesium ions were observed binding to the nucleotide, both ligated in octahedral coordination spheres. In the RmlA/dTDP-glucose complex, only a single magnesium ion was observed. Importantly, for RmlA-type enzymes with known three-dimensional structures, not one model shows the position of the magnesium ion bound to the nucleotide-linked sugar. As such, this investigation represents the first direct observation of the manner in which a magnesium ion is coordinated to the RmlA product and thus has important ramifications for structure-based drug design. In the past, molecular modeling procedures have been employed to derive a three-dimensional model of the M. tuberculosis RmlA for drug design. The X-ray structures presented herein provide a superior molecular scaffold for such endeavors in the treatment of one of the world's deadliest diseases.
The structure of glucose-1-phosphate thymidylyltransferase from Mycobacterium tuberculosis reveals the location of an essential magnesium ion in the RmlA-type enzymes.,Brown HA, Thoden JB, Tipton PA, Holden HM Protein Sci. 2018 Feb;27(2):441-450. doi: 10.1002/pro.3333. Epub 2017 Nov 9. PMID:29076563[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Brown HA, Thoden JB, Tipton PA, Holden HM. The structure of glucose-1-phosphate thymidylyltransferase from Mycobacterium tuberculosis reveals the location of an essential magnesium ion in the RmlA-type enzymes. Protein Sci. 2018 Feb;27(2):441-450. doi: 10.1002/pro.3333. Epub 2017 Nov 9. PMID:29076563 doi:http://dx.doi.org/10.1002/pro.3333
|
