4xgk: Difference between revisions
New page: '''Unreleased structure''' The entry 4xgk is ON HOLD Authors: Wangkanont, K., Heroux, A., Forest, K.T., Kiessling, L.L. Description: Crystal strucutre of UDP-galactopyranose mutase fro... |
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==Crystal structure of UDP-galactopyranose mutase from Corynebacterium diphtheriae in complex with 2-[4-(4-chlorophenyl)-7-(2-thienyl)-2-thia-5,6,8,9-tetrazabicyclo[4.3.0]nona-4,7,9-trien-3-yl]acetic== | |||
<StructureSection load='4xgk' size='340' side='right'caption='[[4xgk]], [[Resolution|resolution]] 2.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4xgk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Corynebacterium_diphtheriae_NCTC_13129 Corynebacterium diphtheriae NCTC 13129]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XGK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XGK 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]] 2.652Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=40K:[(7S)-6-(4-CHLOROPHENYL)-3-(THIOPHEN-2-YL)-7H-[1,2,4]TRIAZOLO[3,4-B][1,3,4]THIADIAZIN-7-YL]ACETIC+ACID'>40K</scene>, <scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</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=4xgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xgk OCA], [https://pdbe.org/4xgk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xgk RCSB], [https://www.ebi.ac.uk/pdbsum/4xgk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xgk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6NER4_CORDI Q6NER4_CORDI] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Galactofuranose (Galf) is present in glycans critical for virulence and viability of several pathogenic microbes, including Mycobacterium tuberculosis, yet the monosaccharide is absent from mammalian glycans. Uridine 5'-diphosphate-galactopyranose mutase (UGM) catalyzes the formation of UDP-Galf, which is required to produce Galf-containing glycoconjugates. Inhibitors of UGM have therefore been sought as antimicrobial leads and to delineate the roles of Galf in cells. Obtaining cell permeable UGM probes by either design or high throughput screens has been difficult, as has elucidating how UGM binds small molecule, non-carbohydrate inhibitors. To address these issues, we employed structure-based virtual screening to uncover new inhibitor chemotypes, including a triazolothiadiazine series. These compounds are among the most potent antimycobacterial UGM inhibitors described. They also facilitated determination of a UGM-small molecule inhibitor structure, which can guide optimization. A comparison of results from the computational screen and a high-throughput fluorescence polarization screen indicated that the scaffold hits from the former had been evaluated in the FP screen but missed. By focusing on promising compounds, the virtual screen rescued false negatives, providing a blueprint for generating new UGM probes and therapeutic leads. | |||
Virtual screening for UDP-galactopyranose mutase ligands identifies a new class of antimycobacterial agents.,Kincaid VA, London N, Wangkanont K, Wesener DA, Marcus SA, Heroux A, Nedyalkova L, Talaat AM, Forest KT, Shoichet BK, Kiessling LL ACS Chem Biol. 2015 Jul 27. PMID:26214585<ref>PMID:26214585</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4xgk" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[UDP-galactopyranose mutase 3D structures|UDP-galactopyranose mutase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Corynebacterium diphtheriae NCTC 13129]] | |||
[[Category: Large Structures]] | |||
[[Category: Forest KT]] | |||
[[Category: Heroux A]] | |||
[[Category: Kiessling LL]] | |||
[[Category: Wangkanont K]] | |||
Latest revision as of 10:45, 27 September 2023
Crystal structure of UDP-galactopyranose mutase from Corynebacterium diphtheriae in complex with 2-[4-(4-chlorophenyl)-7-(2-thienyl)-2-thia-5,6,8,9-tetrazabicyclo[4.3.0]nona-4,7,9-trien-3-yl]aceticCrystal structure of UDP-galactopyranose mutase from Corynebacterium diphtheriae in complex with 2-[4-(4-chlorophenyl)-7-(2-thienyl)-2-thia-5,6,8,9-tetrazabicyclo[4.3.0]nona-4,7,9-trien-3-yl]acetic
Structural highlights
FunctionPublication Abstract from PubMedGalactofuranose (Galf) is present in glycans critical for virulence and viability of several pathogenic microbes, including Mycobacterium tuberculosis, yet the monosaccharide is absent from mammalian glycans. Uridine 5'-diphosphate-galactopyranose mutase (UGM) catalyzes the formation of UDP-Galf, which is required to produce Galf-containing glycoconjugates. Inhibitors of UGM have therefore been sought as antimicrobial leads and to delineate the roles of Galf in cells. Obtaining cell permeable UGM probes by either design or high throughput screens has been difficult, as has elucidating how UGM binds small molecule, non-carbohydrate inhibitors. To address these issues, we employed structure-based virtual screening to uncover new inhibitor chemotypes, including a triazolothiadiazine series. These compounds are among the most potent antimycobacterial UGM inhibitors described. They also facilitated determination of a UGM-small molecule inhibitor structure, which can guide optimization. A comparison of results from the computational screen and a high-throughput fluorescence polarization screen indicated that the scaffold hits from the former had been evaluated in the FP screen but missed. By focusing on promising compounds, the virtual screen rescued false negatives, providing a blueprint for generating new UGM probes and therapeutic leads. Virtual screening for UDP-galactopyranose mutase ligands identifies a new class of antimycobacterial agents.,Kincaid VA, London N, Wangkanont K, Wesener DA, Marcus SA, Heroux A, Nedyalkova L, Talaat AM, Forest KT, Shoichet BK, Kiessling LL ACS Chem Biol. 2015 Jul 27. PMID:26214585[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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