This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


7coz

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 7coz is ON HOLD until Paper Publication
+
==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]] 1.85&Aring;' scene=''>
 +
== Structural highlights ==
 +
<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>
 +
</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='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>
 +
<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>
 +
<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>
 +
</table>
 +
== Function ==
 +
[[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>
 +
<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: Dileep, K.V., Ihara, K., Sakai, N., Shirozu, M., Zhang, K.Y.J.
+
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: Crystal Structure of double mutant Y115E Y117E human Secretory Glutaminyl Cyclase in complex with LSB-41
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Shirozu, M]]
+
<div class="pdbe-citations 7coz" style="background-color:#fffaf0;"></div>
-
[[Category: Zhang, K.Y.J]]
+
== References ==
-
[[Category: Dileep, K.V]]
+
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Glutaminyl-peptide cyclotransferase]]
 +
[[Category: Human]]
 +
[[Category: Large Structures]]
 +
[[Category: Dileep, K V]]
[[Category: Ihara, K]]
[[Category: Ihara, K]]
[[Category: Sakai, N]]
[[Category: Sakai, N]]
 +
[[Category: Shirozu, M]]
 +
[[Category: Zhang, K Y.J]]
 +
[[Category: Alzheimer's disease]]
 +
[[Category: Pyroglutamate]]
 +
[[Category: Sqc]]
 +
[[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

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7coz"
Personal tools