7cp0: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 7cp0 is ON HOLD
+==Crystal Structure of double mutant Y115E Y117E human Secretory Glutaminyl Cyclase==
+<StructureSection load='7cp0' size='340' side='right'caption='[[7cp0]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7cp0]] 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=7CP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CP0 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]] 1.7&#8491;</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=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=7cp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cp0 OCA], [https://pdbe.org/7cp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cp0 RCSB], [https://www.ebi.ac.uk/pdbsum/7cp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cp0 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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7cp0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Glutaminyl cyclase|Glutaminyl cyclase]]
+== 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]]