4hcq
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal structure of GLMU from mycobacterium tuberculosis in complex with glucosamine-1-phosphate== | |
| - | + | <StructureSection load='4hcq' size='340' side='right' caption='[[4hcq]], [[Resolution|resolution]] 2.60Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[4hcq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HCQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HCQ FirstGlance]. <br> | |
| - | ==Function== | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GN1:2-(ACETYLAMINO)-2-DEOXY-1-O-PHOSPHONO-ALPHA-D-GLUCOPYRANOSE'>GN1</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glmU, Rv1018c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</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=4hcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hcq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hcq RCSB], [http://www.ebi.ac.uk/pdbsum/4hcq PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
[[http://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> | [[http://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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU), exclusive to prokaryotes, is a bifunctional enzyme that synthesizes UDP-GlcNAc-an important component of the cell wall of many microorganisms. Uridyltransfer, one of the reactions it catalyzes, involves binding GlcNAc-1-P, UTP and Mg(2+) ions; however, whether one or two ions catalyze this reaction remains ambiguous. Here, we resolve this using biochemical and crystallographic studies on GlmU from Mycobacterium tuberculosis (GlmU(Mtb)) and identify a two-metal-ion mechanism (mechanism-B). In contrast to well-established two-metal mechanism (mechanism-A) for enzymes acting on nucleic acids, mechanism-B is distinct in the way the two Mg(2+) ions (Mg(2+)A and Mg(2+)B) are positioned and stabilized. Further, attempts to delineate the roles of the metal ions in substrate stabilization, nucleophile activation and transition-state stabilization are presented. Interestingly, a detailed analysis of the available structures of sugar nucleotidyl transferases (SNTs) suggests that they too would utilize mechanism-B rather than mechanism-A. Based on this, SNTs could be classified into Group-I, which employs the two-metal mechanism-B as in GlmU, and Group-II that employs a variant one-metal mechanism-B, wherein the role of Mg(2+)A is substituted by a conserved lysine. Strikingly, eukaryotic SNTs appear confined to Group-II. Recognizing these differences may be important in the design of selective inhibitors against microbial nucleotidyl transferases. | ||
| - | + | Crystal structures identify an atypical two-metal-ion mechanism for uridyltransfer in GlmU: its significance to sugar nucleotidyl transferases.,Jagtap PK, Verma SK, Vithani N, Bais VS, Prakash B J Mol Biol. 2013 May 27;425(10):1745-59. doi: 10.1016/j.jmb.2013.02.019. Epub, 2013 Feb 26. PMID:23485416<ref>PMID:23485416</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
| - | [[Category: Jagtap, P K.A | + | [[Category: Jagtap, P K.A]] |
| - | [[Category: Verma, S K | + | [[Category: Verma, S K]] |
| - | [[Category: Vithani, N | + | [[Category: Vithani, N]] |
[[Category: Acetyltransferase]] | [[Category: Acetyltransferase]] | ||
[[Category: Acyltransferase]] | [[Category: Acyltransferase]] | ||
Revision as of 18:35, 25 December 2014
Crystal structure of GLMU from mycobacterium tuberculosis in complex with glucosamine-1-phosphate
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Categories: Mycobacterium tuberculosis | Jagtap, P K.A | Verma, S K | Vithani, N | Acetyltransferase | Acyltransferase | Bifunctional | Cell shape | Cell wall biogenesis/degradation | Left-handed-beta-helix | Magnesium | Metal-binding | Multifunctional enzyme | Nucleotidyltransferase | Peptidoglycan synthesis | Pyrophosphorylase | Rossmann-like fold | Transferase
