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4knx

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Revision as of 09:03, 7 December 2022

Hin GlmU Bound to WG176

Structural highlights

4knx is a 1 chain structure with sequence from Haemophilus influenzae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

Publication Abstract from PubMed

An aminoquinazoline series targeting the essential bacterial enzyme GlmU (uridyltransferase) were previously reported (Biochem. J.2012, 446, 405). In this study, we further explored SAR through a combination of traditional medicinal chemistry and structure-based drug design, resulting in a novel scaffold (benzamide) with selectivity against protein kinases. Virtual screening identified fragments that could be fused into the core scaffold, exploiting additional binding interactions and thus improving potency. These efforts resulted in a hybrid compound with target potency increased by a 1000-fold, while maintaining selectivity against selected protein kinases and an improved level of solubility and protein binding. Despite these significant improvements no significant antibacterial activity was yet observed within this class.

Rational design of inhibitors of the bacterial cell wall synthetic enzyme GlmU using virtual screening and lead-hopping.,Doig P, Boriack-Sjodin PA, Dumas J, Hu J, Itoh K, Johnson K, Kazmirski S, Kinoshita T, Kuroda S, Sato TO, Sugimoto K, Tohyama K, Aoi H, Wakamatsu K, Wang H Bioorg Med Chem. 2014 Sep 16. pii: S0968-0896(14)00604-X. doi:, 10.1016/j.bmc.2014.08.017. PMID:25262942^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mochalkin I, Lightle S, Zhu Y, Ohren JF, Spessard C, Chirgadze NY, Banotai C, Melnick M, McDowell L. Characterization of substrate binding and catalysis in the potential antibacterial target N-acetylglucosamine-1-phosphate uridyltransferase (GlmU). Protein Sci. 2007 Dec;16(12):2657-66. PMID:18029420 doi:http://dx.doi.org/16/12/2657
↑ Doig P, Boriack-Sjodin PA, Dumas J, Hu J, Itoh K, Johnson K, Kazmirski S, Kinoshita T, Kuroda S, Sato TO, Sugimoto K, Tohyama K, Aoi H, Wakamatsu K, Wang H. Rational design of inhibitors of the bacterial cell wall synthetic enzyme GlmU using virtual screening and lead-hopping. Bioorg Med Chem. 2014 Sep 16. pii: S0968-0896(14)00604-X. doi:, 10.1016/j.bmc.2014.08.017. PMID:25262942 doi:http://dx.doi.org/10.1016/j.bmc.2014.08.017

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4knx"

Categories: Haemophilus influenzae | Large Structures | Boriack-Sjodin PA | Doig P | Kazmirski SL

@@ Line 3: / Line 3: @@
 <StructureSection load='4knx' size='340' side='right'caption='[[4knx]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4knx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_influenzae"_lehmann_and_neumann_1896 "bacterium influenzae" lehmann and neumann 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KNX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KNX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4knx]] 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=4KNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KNX FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1S9:[(4-{[4-(BENZOYLAMINO)PHENYL]AMINO}-6-METHOXYQUINAZOLIN-7-YL)OXY]ACETIC+ACID'>1S9</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1S9:[(4-{[4-(BENZOYLAMINO)PHENYL]AMINO}-6-METHOXYQUINAZOLIN-7-YL)OXY]ACETIC+ACID'>1S9</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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">[[4knr|4knr]], [[4kpx|4kpx]], [[4kpz|4kpz]], [[4kql|4kql]]</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=4knx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4knx OCA], [https://pdbe.org/4knx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4knx RCSB], [https://www.ebi.ac.uk/pdbsum/4knx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4knx ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glmU, HI_0642 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=727 "Bacterium influenzae" Lehmann and Neumann 1896])</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=4knx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4knx OCA], [http://pdbe.org/4knx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4knx RCSB], [http://www.ebi.ac.uk/pdbsum/4knx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4knx ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 18: @@
 </div>
 <div class="pdbe-citations 4knx" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[N-acetylglucosamine-1-phosphate uridyltransferase|N-acetylglucosamine-1-phosphate uridyltransferase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bacterium influenzae lehmann and neumann 1896]]
+[[Category: Haemophilus influenzae]]
 [[Category: Large Structures]]
-[[Category: Boriack-Sjodin, P A]]
+[[Category: Boriack-Sjodin PA]]
-[[Category: Doig, P]]
+[[Category: Doig P]]
-[[Category: Kazmirski, S L]]
+[[Category: Kazmirski SL]]
-[[Category: Beta helix]]
-[[Category: Cell wall biosynthesis]]
-[[Category: Inhibitor bound]]
-[[Category: Transferase-transferase inhibitor complex]]

4knx

From Proteopedia

Revision as of 09:03, 7 December 2022

Hin GlmU Bound to WG176

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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