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[[Image:2v0h.jpg|left|200px]]
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{{STRUCTURE_2v0h|  PDB=2v0h  |  SCENE=  }}
'''CHARACTERIZATION OF SUBSTRATE BINDING AND CATALYSIS OF THE POTENTIAL ANTIBACTERIAL TARGET N-ACETYLGLUCOSAMINE-1-PHOSPHATE URIDYLTRANSFERASE (GLMU)'''


==Characterization of Substrate Binding and Catalysis of the Potential Antibacterial Target N-acetylglucosamine-1-phosphate Uridyltransferase (GlmU)==
<StructureSection load='2v0h' size='340' side='right'caption='[[2v0h]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2v0h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemophilus_influenzae Haemophilus influenzae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V0H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V0H FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.79&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2v0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v0h OCA], [https://pdbe.org/2v0h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v0h RCSB], [https://www.ebi.ac.uk/pdbsum/2v0h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v0h ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLMU_HAEIN GLMU_HAEIN] 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:18029420</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v0/2v0h_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2v0h ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) catalyzes the first step in peptidoglycan biosynthesis in both Gram-positive and Gram-negative bacteria. The products of the GlmU reaction are essential for bacterial survival, making this enzyme an attractive target for antibiotic drug discovery. A series of Haemophilus influenzae GlmU (hiGlmU) structures were determined by X-ray crystallography in order to provide structural and functional insights into GlmU activity and inhibition. The information derived from these structures was combined with biochemical characterization of the K25A, Q76A, D105A, Y103A, V223A, and E224A hiGlmU mutants in order to map these active-site residues to catalytic activity of the enzyme and refine the mechanistic model of the GlmU uridyltransferase reaction. These studies suggest that GlmU activity follows a sequential substrate-binding order that begins with UTP binding noncovalently to the GlmU enzyme. The uridyltransferase active site then remains in an open apo-like conformation until N-acetylglucosamine-1-phosphate (GlcNAc-1-P) binds and induces a conformational change at the GlcNAc-binding subsite. Following the binding of GlcNAc-1-P to the UTP-charged uridyltransferase active site, the non-esterified oxygen of GlcNAc-1-P performs a nucleophilic attack on the alpha-phosphate group of UTP. The new data strongly suggest that the mechanism of phosphotransfer in the uridyltransferase reaction in GlmU is primarily through an associative mechanism with a pentavalent phosphate intermediate and an inversion of stereochemistry. Finally, the structural and biochemical characterization of the uridyltransferase active site and catalytic mechanism described herein provides a basis for the structure-guided design of novel antibacterial agents targeting GlmU activity.


==Overview==
Characterization of substrate binding and catalysis in the potential antibacterial target N-acetylglucosamine-1-phosphate uridyltransferase (GlmU).,Mochalkin I, Lightle S, Zhu Y, Ohren JF, Spessard C, Chirgadze NY, Banotai C, Melnick M, McDowell L Protein Sci. 2007 Dec;16(12):2657-66. PMID:18029420<ref>PMID:18029420</ref>
N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) catalyzes the first step in peptidoglycan biosynthesis in both Gram-positive and Gram-negative bacteria. The products of the GlmU reaction are essential for bacterial survival, making this enzyme an attractive target for antibiotic drug discovery. A series of Haemophilus influenzae GlmU (hiGlmU) structures were determined by X-ray crystallography in order to provide structural and functional insights into GlmU activity and inhibition. The information derived from these structures was combined with biochemical characterization of the K25A, Q76A, D105A, Y103A, V223A, and E224A hiGlmU mutants in order to map these active-site residues to catalytic activity of the enzyme and refine the mechanistic model of the GlmU uridyltransferase reaction. These studies suggest that GlmU activity follows a sequential substrate-binding order that begins with UTP binding noncovalently to the GlmU enzyme. The uridyltransferase active site then remains in an open apo-like conformation until N-acetylglucosamine-1-phosphate (GlcNAc-1-P) binds and induces a conformational change at the GlcNAc-binding subsite. Following the binding of GlcNAc-1-P to the UTP-charged uridyltransferase active site, the non-esterified oxygen of GlcNAc-1-P performs a nucleophilic attack on the alpha-phosphate group of UTP. The new data strongly suggest that the mechanism of phosphotransfer in the uridyltransferase reaction in GlmU is primarily through an associative mechanism with a pentavalent phosphate intermediate and an inversion of stereochemistry. Finally, the structural and biochemical characterization of the uridyltransferase active site and catalytic mechanism described herein provides a basis for the structure-guided design of novel antibacterial agents targeting GlmU activity.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2V0H is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Haemophilus_influenzae Haemophilus influenzae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V0H OCA].
</div>
<div class="pdbe-citations 2v0h" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Characterization of substrate binding and catalysis in the potential antibacterial target N-acetylglucosamine-1-phosphate uridyltransferase (GlmU)., Mochalkin I, Lightle S, Zhu Y, Ohren JF, Spessard C, Chirgadze NY, Banotai C, Melnick M, McDowell L, Protein Sci. 2007 Dec;16(12):2657-66. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18029420 18029420]
*[[N-acetylglucosamine-1-phosphate uridyltransferase|N-acetylglucosamine-1-phosphate uridyltransferase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Haemophilus influenzae]]
[[Category: Haemophilus influenzae]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Chirgadze, N.]]
[[Category: Chirgadze NY]]
[[Category: Lightle, S.]]
[[Category: Lightle S]]
[[Category: Mochalkin, I.]]
[[Category: Mochalkin I]]
[[Category: Ohren, J.]]
[[Category: Ohren JF]]
[[Category: Acyltransferase]]
[[Category: Associative mechanism]]
[[Category: Cell shape]]
[[Category: Cell wall]]
[[Category: Glmu]]
[[Category: Magnesium]]
[[Category: Metal-binding]]
[[Category: Multifunctional enzyme]]
[[Category: Nucleotidyltransferase]]
[[Category: Peptidoglycan synthesis]]
[[Category: Transferase]]
[[Category: Uridylation]]
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