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7slx
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7slx is ON HOLD until Paper Publication Authors: Vajdos, F.F. Description: Vanin-1 complexed with Compound 11 Category: Unreleased Structures [...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Vanin-1 complexed with Compound 11== | |
| + | <StructureSection load='7slx' size='340' side='right'caption='[[7slx]], [[Resolution|resolution]] 2.35Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7slx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SLX FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9SS:(3R)-1-(2-{[1-(pyrimidin-5-yl)cyclopropyl]amino}pyrimidine-5-carbonyl)piperidine-3-carbonitrile'>9SS</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pantetheine_hydrolase Pantetheine hydrolase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.92 3.5.1.92] </span></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=7slx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7slx OCA], [https://pdbe.org/7slx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7slx RCSB], [https://www.ebi.ac.uk/pdbsum/7slx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7slx ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/VNN1_HUMAN VNN1_HUMAN]] Amidohydrolase that hydrolyzes specifically one of the carboamide linkages in D-pantetheine thus recycling pantothenic acid (vitamin B5) and releasing cysteamine.<ref>PMID:10567687</ref> <ref>PMID:11491533</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe 2 that was used to build target confidence, concerns over the ketone moiety led to the replacement of this group. The successful replacement of this moiety was achieved with pyrimidine carboxamides derived from cyclic secondary amines that were extensively characterized using biophysical and crystallographic methods as competitive inhibitors of vanin-1. Through optimization of potency and physicochemical and ADME properties, and guided by co-crystal structures with vanin-1, 3 was identified with a suitable profile for advancement into preclinical development. | ||
| - | + | Discovery of a Series of Pyrimidine Carboxamides as Inhibitors of Vanin-1.,Casimiro-Garcia A, Allais C, Brennan A, Choi C, Dower G, Farley KA, Fleming M, Flick A, Frisbie RK, Hall J, Hepworth D, Jones H, Knafels JD, Kortum S, Lovering FE, Mathias JP, Mohan S, Morgan PM, Parng C, Parris K, Pullen N, Schlerman F, Stansfield J, Strohbach JW, Vajdos FF, Vincent F, Wang H, Wang X, Webster R, Wright SW J Med Chem. 2021 Dec 30. doi: 10.1021/acs.jmedchem.1c01849. PMID:34967602<ref>PMID:34967602</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Vajdos, F | + | <div class="pdbe-citations 7slx" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Pantetheine hydrolase]] | ||
| + | [[Category: Vajdos, F F]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Pantetheine]] | ||
| + | [[Category: Pyrimdine carboxamide]] | ||
| + | [[Category: Sbdd]] | ||
Current revision
Vanin-1 complexed with Compound 11
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