6ge9: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6ge9' size='340' side='right' caption='[[6ge9]], [[Resolution|resolution]] 2.26Å' scene=''> | <StructureSection load='6ge9' size='340' side='right' caption='[[6ge9]], [[Resolution|resolution]] 2.26Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ge9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GE9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GE9 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ge9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycta Mycta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GE9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GE9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=G1P:ALPHA-D-GLUCOSE-1-PHOSPHATE'>G1P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=G1P:ALPHA-D-GLUCOSE-1-PHOSPHATE'>G1P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glmU, MRA_1026 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=419947 MYCTA])</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=6ge9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ge9 OCA], [http://pdbe.org/6ge9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ge9 RCSB], [http://www.ebi.ac.uk/pdbsum/6ge9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ge9 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=6ge9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ge9 OCA], [http://pdbe.org/6ge9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ge9 RCSB], [http://www.ebi.ac.uk/pdbsum/6ge9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ge9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 22: | Line 23: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Mycta]] | |||
[[Category: Argyrou, A]] | [[Category: Argyrou, A]] | ||
[[Category: Carvalho, L P.S de]] | [[Category: Carvalho, L P.S de]] | ||
Latest revision as of 09:02, 27 June 2018
Structure of Mycobacterium tuberculosis GlmU bound to Glc-1P and Ac-CoAStructure of Mycobacterium tuberculosis GlmU bound to Glc-1P and Ac-CoA
Structural highlights
Function[GLMU_MYCTA] 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 (By similarity). Publication Abstract from PubMedThe biosynthetic pathway of peptidoglycan is essential for Mycobacterium tuberculosis. We report here the acetyltransferase substrate specificity and catalytic mechanism of the bifunctional N-acetyltransferase/uridylyltransferase from M. tuberculosis (GlmU). This enzyme is responsible for the final two steps of the synthesis of UDP- N-acetylglucosamine, which is an essential precursor of peptidoglycan, from glucosamine 1-phosphate, acetyl-coenzyme A, and uridine 5'-triphosphate. GlmU utilizes ternary complex formation to transfer an acetyl from acetyl-coenzyme A to glucosamine 1-phosphate to form N-acetylglucosamine 1-phosphate. Steady-state kinetic studies and equilibrium binding experiments indicate that GlmU follows a steady-state ordered kinetic mechanism, with acetyl-coenzyme A binding first, which triggers a conformational change in GlmU, followed by glucosamine 1-phosphate binding. Coenzyme A is the last product to dissociate. Chemistry is partially rate-limiting as indicated by pH-rate studies and solvent kinetic isotope effects. A novel crystal structure of a mimic of the Michaelis complex, with glucose 1-phosphate and acetyl-coenzyme A, helps us to propose the residues involved in deprotonation of glucosamine 1-phosphate and the loop movement that likely generates the active site required for glucosamine 1-phosphate to bind. Together, these results pave the way for the rational discovery of improved inhibitors against M. tuberculosis GlmU, some of which might become candidates for antibiotic discovery programs. The Mechanism of Acetyl Transfer Catalyzed by Mycobacterium tuberculosis GlmU.,Craggs PD, Mouilleron S, Rejzek M, de Chiara C, Young RJ, Field RA, Argyrou A, de Carvalho LPS Biochemistry. 2018 May 2. doi: 10.1021/acs.biochem.8b00121. PMID:29684272[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||