3pb4: Difference between revisions

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<StructureSection load='3pb4' size='340' side='right'caption='[[3pb4]], [[Resolution|resolution]] 1.13&Aring;' scene=''>
<StructureSection load='3pb4' size='340' side='right'caption='[[3pb4]], [[Resolution|resolution]] 1.13&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3pb4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PB4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3pb4]] is a 1 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=3PB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PB4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.13&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3pb6|3pb6]], [[3pb7|3pb7]], [[3pb8|3pb8]], [[3pb9|3pb9]], [[3pbb|3pbb]], [[3pbe|3pbe]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">QPCTL ([https://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'>[https://en.wikipedia.org/wiki/Glutaminyl-peptide_cyclotransferase Glutaminyl-peptide cyclotransferase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3pb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pb4 OCA], [https://pdbe.org/3pb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pb4 RCSB], [https://www.ebi.ac.uk/pdbsum/3pb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pb4 ProSAT]</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=3pb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pb4 OCA], [https://pdbe.org/3pb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pb4 RCSB], [https://www.ebi.ac.uk/pdbsum/3pb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pb4 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/QPCTL_HUMAN QPCTL_HUMAN]] Responsible for the biosynthesis of pyroglutamyl peptides.<ref>PMID:18486145</ref> <ref>PMID:21288892</ref>
[https://www.uniprot.org/uniprot/QPCTL_HUMAN QPCTL_HUMAN] Responsible for the biosynthesis of pyroglutamyl peptides.<ref>PMID:18486145</ref> <ref>PMID:21288892</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Aberrant pyroglutamate formation at the N terminus of certain peptides and proteins, catalyzed by glutaminyl cyclases (QCs), is linked to some pathological conditions, such as Alzheimer disease. Recently, a glutaminyl cyclase (QC) inhibitor, PBD150, was shown to be able to reduce the deposition of pyroglutamate-modified amyloid-beta peptides in brain of transgenic mouse models of Alzheimer disease, leading to a significant improvement of learning and memory in those transgenic animals. Here, we report the 1.05-1.40 A resolution structures, solved by the sulfur single-wavelength anomalous dispersion phasing method, of the Golgi-luminal catalytic domain of the recently identified Golgi-resident QC (gQC) and its complex with PBD150. We also describe the high-resolution structures of secretory QC (sQC)-PBD150 complex and two other gQC-inhibitor complexes. gQC structure has a scaffold similar to that of sQC but with a relatively wider and negatively charged active site, suggesting a distinct substrate specificity from sQC. Upon binding to PBD150, a large loop movement in gQC allows the inhibitor to be tightly held in its active site primarily by hydrophobic interactions. Further comparisons of the inhibitor-bound structures revealed distinct interactions of the inhibitors with gQC and sQC, which are consistent with the results from our inhibitor assays reported here. Because gQC and sQC may play different biological roles in vivo, the different inhibitor binding modes allow the design of specific inhibitors toward gQC and sQC.


Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding.,Huang KF, Liaw SS, Huang WL, Chia CY, Lo YC, Chen YL, Wang AH J Biol Chem. 2011 Apr 8;286(14):12439-49. Epub 2011 Feb 1. PMID:21288892<ref>PMID:21288892</ref>
==See Also==
 
*[[Glutaminyl cyclase|Glutaminyl cyclase]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3pb4" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Glutaminyl-peptide cyclotransferase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Chen, Y L]]
[[Category: Chen YL]]
[[Category: Chia, C Y]]
[[Category: Chia CY]]
[[Category: Huang, K F]]
[[Category: Huang KF]]
[[Category: Huang, W L]]
[[Category: Huang WL]]
[[Category: Liaw, S S]]
[[Category: Liaw SS]]
[[Category: Lo, Y C]]
[[Category: Lo YC]]
[[Category: Wang, A H.J]]
[[Category: Wang AHJ]]
[[Category: Alpha/beta protein]]
[[Category: Alpha/beta-mixed fold]]
[[Category: Glutaminyl cyclase]]
[[Category: Golgi membrane]]
[[Category: Transferase]]

Latest revision as of 16:30, 1 March 2024

Crystal structure of the catalytic domain of human Golgi-resident glutaminyl cyclase at pH 6.0Crystal structure of the catalytic domain of human Golgi-resident glutaminyl cyclase at pH 6.0

Structural highlights

3pb4 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.13Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

QPCTL_HUMAN Responsible for the biosynthesis of pyroglutamyl peptides.[1] [2]

See Also

References

  1. ↑ Cynis H, Rahfeld JU, Stephan A, Kehlen A, Koch B, Wermann M, Demuth HU, Schilling S. Isolation of an isoenzyme of human glutaminyl cyclase: retention in the Golgi complex suggests involvement in the protein maturation machinery. J Mol Biol. 2008 Jun 20;379(5):966-80. doi: 10.1016/j.jmb.2008.03.078. Epub 2008 , Apr 15. PMID:18486145 doi:http://dx.doi.org/10.1016/j.jmb.2008.03.078
  2. ↑ Huang KF, Liaw SS, Huang WL, Chia CY, Lo YC, Chen YL, Wang AH. Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding. J Biol Chem. 2011 Apr 8;286(14):12439-49. Epub 2011 Feb 1. PMID:21288892 doi:10.1074/jbc.M110.208595

3pb4, resolution 1.13Å

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