|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Glutamate Racemase (MurI) from Mycobacterium smegmatis with bound D-glutamate, 1.8 Angstrom resolution, X-ray diffraction== | | ==Glutamate Racemase (MurI) from Mycobacterium smegmatis with bound D-glutamate, 1.8 Angstrom resolution, X-ray diffraction== |
| - | <StructureSection load='5ijw' size='340' side='right' caption='[[5ijw]], [[Resolution|resolution]] 1.76Å' scene=''> | + | <StructureSection load='5ijw' size='340' side='right'caption='[[5ijw]], [[Resolution|resolution]] 1.76Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ijw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IJW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IJW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ijw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IJW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]] 1.76Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hj7|5hj7]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">murI, MSMEG_4903, MSMEI_4776 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</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=5ijw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ijw OCA], [https://pdbe.org/5ijw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ijw RCSB], [https://www.ebi.ac.uk/pdbsum/5ijw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ijw ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamate_racemase Glutamate racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.3 5.1.1.3] </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=5ijw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ijw OCA], [http://pdbe.org/5ijw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ijw RCSB], [http://www.ebi.ac.uk/pdbsum/5ijw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ijw ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MURI_MYCS2 MURI_MYCS2]] Provides the (R)-glutamate required for cell wall biosynthesis. | + | [https://www.uniprot.org/uniprot/MURI_MYCS2 MURI_MYCS2] Provides the (R)-glutamate required for cell wall biosynthesis. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 5ijw" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5ijw" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glutamate racemase 3D structures|Glutamate racemase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutamate racemase]] | + | [[Category: Large Structures]] |
| - | [[Category: Mycs2]] | + | [[Category: Mycolicibacterium smegmatis MC2 155]] |
| - | [[Category: Krause, K]] | + | [[Category: Krause K]] |
| - | [[Category: Nakatani, Y]] | + | [[Category: Nakatani Y]] |
| - | [[Category: Poen, S]] | + | [[Category: Poen S]] |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Kinetic]]
| + | |
| - | [[Category: Side-to-side dimer]]
| + | |
| - | [[Category: Tuberculosis drug design]]
| + | |
| Structural highlights
Function
MURI_MYCS2 Provides the (R)-glutamate required for cell wall biosynthesis.
Publication Abstract from PubMed
Glutamate racemase (MurI) is responsible for providing D-glutamate for peptidoglycan biosynthesis in bacteria and has been a favoured target in pharmaceutical drug design efforts. It has recently been proven to be essential in Mycobacterium tuberculosis, the causative organism of tuberculosis, a disease for which new medications are urgently needed. In the present study, we have determined the protein crystal structures of MurI from both M. tuberculosis and Mycobacterium smegmatis in complex with D-glutamate to 2.3 A and 1.8 A resolution respectively. These structures are conserved, but reveal differences in their active site architecture compared with that of other MurI structures. Furthermore, compounds designed to target other glutamate racemases have been screened but do not inhibit mycobacterial MurI, suggesting that a new drug design effort will be needed to develop inhibitors. A new type of MurI dimer arrangement has been observed in both structures, and this arrangement becomes the third biological dimer geometry for MurI found to date. The mycobacterial MurI dimer is tightly associated, with a KD in the nanomolar range. The enzyme binds D- and L-glutamate specifically, but is inactive in solution unless the dimer interface is mutated. We created triple mutants of this interface in the M. smegmatis glutamate racemase (D26R/R105A/G194R or E) that have appreciable activity (kcat=0.056-0.160 min(-1) and KM=0.26-0.51 mM) and can be utilized to screen proposed antimicrobial candidates for inhibition.
Exploring the structure of glutamate racemase from Mycobacterium tuberculosis as a template for anti-mycobacterial drug discovery.,Poen S, Nakatani Y, Opel-Reading HK, Lasse M, Dobson RC, Krause KL Biochem J. 2016 May 1;473(9):1267-80. doi: 10.1042/BCJ20160186. Epub 2016 Mar 10. PMID:26964898[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Poen S, Nakatani Y, Opel-Reading HK, Lasse M, Dobson RC, Krause KL. Exploring the structure of glutamate racemase from Mycobacterium tuberculosis as a template for anti-mycobacterial drug discovery. Biochem J. 2016 May 1;473(9):1267-80. doi: 10.1042/BCJ20160186. Epub 2016 Mar 10. PMID:26964898 doi:http://dx.doi.org/10.1042/BCJ20160186
|
