7coz
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7coz is ON HOLD Authors: Dileep, K.V., Ihara, K., Sakai, N., Shirozu, M., Zhang, K.Y.J. Description: Crystal Structure of double mutant Y115E Y117E...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of double mutant Y115E Y117E human Secretory Glutaminyl Cyclase in complex with LSB-41== | |
| + | <StructureSection load='7coz' size='340' side='right'caption='[[7coz]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7coz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7COZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7COZ 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]] 1.85Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=Q39:1-[3-(2-methyl-4-thiophen-2-yl-1,3-thiazol-5-yl)propanoyl]piperidine-4-carboxamide'>Q39</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7coz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7coz OCA], [https://pdbe.org/7coz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7coz RCSB], [https://www.ebi.ac.uk/pdbsum/7coz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7coz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/QPCT_HUMAN QPCT_HUMAN] Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. Also catalyzes N-terminal pyroglutamate formation. In vitro, catalyzes pyroglutamate formation of N-terminally truncated form of APP amyloid-beta peptides [Glu-3]-beta-amyloid. May be involved in the N-terminal pyroglutamate formation of several amyloid-related plaque-forming peptides.<ref>PMID:15063747</ref> <ref>PMID:18486145</ref> <ref>PMID:21288892</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Alzheimer's disease (AD), a common chronic neurodegenerative disease, has become a major public health concern. Despite years of research, therapeutics for AD are limited. Overexpression of secretory glutaminyl cyclase (sQC) in AD brain leads to the formation of a highly neurotoxic pyroglutamate variant of amyloid beta, pGlu-Abeta, which acts as a potential seed for the aggregation of full length Abeta. Preventing the formation of pGlu-Abeta through inhibition of sQC has become an attractive disease-modifying therapy in AD. In this current study, through a pharmacophore assisted high throughput virtual screening, we report a novel sQC inhibitor (Cpd-41) with a piperidine-4-carboxamide moiety (IC50 = 34 muM). Systematic molecular docking, MD simulations and X-ray crystallographic analysis provided atomistic details of the binding of Cpd-41 in the active site of sQC. The unique mode of binding and moderate toxicity of Cpd-41 make this molecule an attractive candidate for designing high affinity sQC inhibitors. | ||
| - | + | Piperidine-4-carboxamide as a new scaffold for designing secretory glutaminyl cyclase inhibitors.,Dileep KV, Sakai N, Ihara K, Kato-Murayama M, Nakata A, Ito A, Sivaraman DM, Shin JW, Yoshida M, Shirouzu M, Zhang KYJ Int J Biol Macromol. 2020 Dec 27;170:415-423. doi:, 10.1016/j.ijbiomac.2020.12.118. PMID:33373636<ref>PMID:33373636</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 7coz" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: Sakai | + | *[[Glutaminyl cyclase|Glutaminyl cyclase]] |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Dileep KV]] | ||
| + | [[Category: Ihara K]] | ||
| + | [[Category: Sakai N]] | ||
| + | [[Category: Shirozu M]] | ||
| + | [[Category: Zhang KYJ]] | ||
Current revision
Crystal Structure of double mutant Y115E Y117E human Secretory Glutaminyl Cyclase in complex with LSB-41
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Categories: Homo sapiens | Large Structures | Dileep KV | Ihara K | Sakai N | Shirozu M | Zhang KYJ
