4aaw: Difference between revisions
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[[ | ==S.pneumoniae GlmU in complex with an antibacterial inhibitor== | ||
<StructureSection load='4aaw' size='340' side='right' caption='[[4aaw]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4aaw]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AAW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4aa7|4aa7]]</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=4aaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aaw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4aaw RCSB], [http://www.ebi.ac.uk/pdbsum/4aaw PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Streptococcus pneumoniae]] | [[Category: Streptococcus pneumoniae]] | ||
[[Category: Breed, J | [[Category: Breed, J]] | ||
[[Category: Ogg, D J | [[Category: Ogg, D J]] | ||
[[Category: Otterbein, L | [[Category: Otterbein, L]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Transferase inhibitor complex]] | [[Category: Transferase inhibitor complex]] | ||
Revision as of 12:08, 25 December 2014
S.pneumoniae GlmU in complex with an antibacterial inhibitor
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