View source for 4aaw


==S.pneumoniae GlmU in complex with an antibacterial inhibitor==
<StructureSection load='4aaw' size='340' side='right'caption='[[4aaw]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4aaw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AAW 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=R84:4-{[1-(2-{[({5-[(3-CARBOXYPROPANOYL)AMINO]-2,4-DIMETHOXYPHENYL}SULFONYL)AMINO]METHYL}PHENYL)PIPERIDIN-4-YL]METHOXY}-4-OXOBUTANOIC+ACID'>R84</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=4aaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aaw OCA], [https://pdbe.org/4aaw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aaw RCSB], [https://www.ebi.ac.uk/pdbsum/4aaw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aaw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLMU_STRR6 GLMU_STRR6] 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).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A novel arylsulfonamide-containing series of compounds represented by 1, discovered by highthroughput screening, inhibit the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetylt ransferase (GlmU). X-ray structure determination confirmed that inhibitor binds at the site occupied by acetyl-CoA, indicating that series is competitive with this substrate. This letter documents our early hit-to-lead evaluation of the chemical series and some of the findings that led to improvement in in-vitro potency against Gram-negative and Gram-positive bacterial isozymes, exemplified by compound 40.

Inhibitors of acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetylt ransferase (GlmU). Part 1: Hit to lead evaluation of a novel arylsulfonamide series.,Green OM, McKenzie AR, Shapiro AB, Otterbein L, Ni H, Patten A, Stokes S, Albert R, Kawatkar S, Breed J Bioorg Med Chem Lett. 2012 Feb 15;22(4):1510-9. Epub 2012 Jan 14. PMID:22297115<ref>PMID:22297115</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4aaw" style="background-color:#fffaf0;"></div>

==See Also==
*[[N-acetylglucosamine-1-phosphate uridyltransferase|N-acetylglucosamine-1-phosphate uridyltransferase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pneumoniae]]
[[Category: Breed J]]
[[Category: Ogg DJ]]
[[Category: Otterbein L]]