4kpx

From Proteopedia

(Difference between revisions)

Revision as of 00:13, 5 August 2016

Hin GlmU bound to WG766

Structural highlights

4kpx is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	4knr, 4knx, 4kpz, 4kql
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 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Hin GlmU bound to WG766==
 <StructureSection load='4kpx' size='340' side='right' caption='[[4kpx]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1SE:N-{4-[(4-HYDROXY-3-NITROBENZOYL)AMINO]PHENYL}PYRIDINE-2-CARBOXAMIDE'>1SE</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]], [[4knx|4knx]], [[4kpz|4kpz]], [[4kql|4kql]]</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=4kpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kpx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kpx RCSB], [http://www.ebi.ac.uk/pdbsum/4kpx PDBsum]</span></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=4kpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kpx OCA], [http://pdbe.org/4kpx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kpx RCSB], [http://www.ebi.ac.uk/pdbsum/4kpx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kpx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4kpx" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4kpx

From Proteopedia

Revision as of 00:13, 5 August 2016

Hin GlmU bound to WG766

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox