7coz

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'''Unreleased structure'''
 
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The entry 7coz is ON HOLD until Paper Publication
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==Crystal Structure of double mutant Y115E Y117E human Secretory Glutaminyl Cyclase in complex with LSB-41==
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<StructureSection load='7coz' size='340' side='right'caption='[[7coz]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7coz]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=7COZ FirstGlance]. <br>
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</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>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">QPCT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutaminyl-peptide_cyclotransferase Glutaminyl-peptide cyclotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.5 2.3.2.5] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7coz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7coz OCA], [http://pdbe.org/7coz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7coz RCSB], [http://www.ebi.ac.uk/pdbsum/7coz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7coz ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[http://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors: Dileep, K.V., Ihara, K., Sakai, N., Shirozu, M., Zhang, K.Y.J.
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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>
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Description: Crystal Structure of double mutant Y115E Y117E human Secretory Glutaminyl Cyclase in complex with LSB-41
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Shirozu, M]]
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<div class="pdbe-citations 7coz" style="background-color:#fffaf0;"></div>
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[[Category: Zhang, K.Y.J]]
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== References ==
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[[Category: Dileep, K.V]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Glutaminyl-peptide cyclotransferase]]
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[[Category: Human]]
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[[Category: Large Structures]]
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[[Category: Dileep, K V]]
[[Category: Ihara, K]]
[[Category: Ihara, K]]
[[Category: Sakai, N]]
[[Category: Sakai, N]]
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[[Category: Shirozu, M]]
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[[Category: Zhang, K Y.J]]
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[[Category: Alzheimer's disease]]
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[[Category: Pyroglutamate]]
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[[Category: Sqc]]
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[[Category: Transferase]]

Revision as of 05:55, 20 January 2021

Crystal Structure of double mutant Y115E Y117E human Secretory Glutaminyl Cyclase in complex with LSB-41

PDB ID 7coz

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OCA

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