|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2qkx' size='340' side='right'caption='[[2qkx]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='2qkx' size='340' side='right'caption='[[2qkx]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qkx]] 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=2QKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QKX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qkx]] is a 1 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=2QKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QKX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GN1:2-(ACETYLAMINO)-2-DEOXY-1-O-PHOSPHONO-ALPHA-D-GLUCOPYRANOSE'>GN1</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]] 2.75Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glmU, Rv1018c, MT1046 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GN1:2-(ACETYLAMINO)-2-DEOXY-1-O-PHOSPHONO-ALPHA-D-GLUCOPYRANOSE'>GN1</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glucosamine-1-phosphate_N-acetyltransferase Glucosamine-1-phosphate N-acetyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.157 2.3.1.157] </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=2qkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qkx OCA], [https://pdbe.org/2qkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qkx RCSB], [https://www.ebi.ac.uk/pdbsum/2qkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qkx 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=2qkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qkx OCA], [https://pdbe.org/2qkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qkx RCSB], [https://www.ebi.ac.uk/pdbsum/2qkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qkx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GLMU_MYCTU GLMU_MYCTU]] Catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-N-acetylglucosamine (UDP-GlcNAc). The C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate (GlcN-1-P) to produce N-acetylglucosamine-1-phosphate (GlcNAc-1-P), which is converted into UDP-GlcNAc by the transfer of uridine 5-monophosphate (from uridine 5-triphosphate), a reaction catalyzed by the N-terminal domain.<ref>PMID:19237750</ref> <ref>PMID:19121323</ref>
| + | [https://www.uniprot.org/uniprot/GLMU_MYCTU GLMU_MYCTU] Catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-N-acetylglucosamine (UDP-GlcNAc). The C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate (GlcN-1-P) to produce N-acetylglucosamine-1-phosphate (GlcNAc-1-P), which is converted into UDP-GlcNAc by the transfer of uridine 5-monophosphate (from uridine 5-triphosphate), a reaction catalyzed by the N-terminal domain.<ref>PMID:19237750</ref> <ref>PMID:19121323</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 37: |
Line 36: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glucosamine-1-phosphate N-acetyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mycobacterium tuberculosis]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Baker, E N]] | + | [[Category: Baker EN]] |
| - | [[Category: Squire, C J]] | + | [[Category: Squire CJ]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Zhang Z]] |
| - | [[Category: Zhang, Z]] | + | |
| - | [[Category: Beta-helix]]
| + | |
| - | [[Category: Rossmann]]
| + | |
| - | [[Category: Substrate complex]]
| + | |
| - | [[Category: Tbsgc]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
GLMU_MYCTU Catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-N-acetylglucosamine (UDP-GlcNAc). The C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate (GlcN-1-P) to produce N-acetylglucosamine-1-phosphate (GlcNAc-1-P), which is converted into UDP-GlcNAc by the transfer of uridine 5-monophosphate (from uridine 5-triphosphate), a reaction catalyzed by the N-terminal domain.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Antibiotic resistance is a major issue in the treatment of infectious diseases such as tuberculosis. Existing antibiotics target only a few cellular pathways and there is an urgent need for antibiotics that have novel molecular mechanisms. The glmU gene is essential in Mycobacterium tuberculosis, being required for optimal bacterial growth, and has been selected as a possible drug target for structural and functional investigation. GlmU is a bifunctional acetyltransferase/uridyltransferase that catalyses the formation of UDP-GlcNAc from GlcN-1-P. UDP-GlcNAc is a substrate for two important biosynthetic pathways: lipopolysaccharide and peptidoglycan synthesis. The crystal structure of M. tuberculosis GlmU has been determined in an unliganded form and in complex with GlcNAc-1-P or UDP-GlcNAc. The structures reveal the residues that are responsible for substrate binding. Enzyme activities were characterized by (1)H NMR and suggest that the presence of acetyl-coenzyme A has an inhibitory effect on uridyltransferase activity.
Structure and function of GlmU from Mycobacterium tuberculosis.,Zhang Z, Bulloch EM, Bunker RD, Baker EN, Squire CJ Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):275-83. Epub 2009, Feb 20. PMID:19237750[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang Z, Bulloch EM, Bunker RD, Baker EN, Squire CJ. Structure and function of GlmU from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):275-83. Epub 2009, Feb 20. PMID:19237750 doi:10.1107/S0907444909001036
- ↑ Parikh A, Verma SK, Khan S, Prakash B, Nandicoori VK. PknB-mediated phosphorylation of a novel substrate, N-acetylglucosamine-1-phosphate uridyltransferase, modulates its acetyltransferase activity. J Mol Biol. 2009 Feb 20;386(2):451-64. Epub 2008 Dec 24. PMID:19121323 doi:10.1016/j.jmb.2008.12.031
- ↑ Zhang Z, Bulloch EM, Bunker RD, Baker EN, Squire CJ. Structure and function of GlmU from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):275-83. Epub 2009, Feb 20. PMID:19237750 doi:10.1107/S0907444909001036
|
