7d23: Difference between revisions
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==Crystal structure of Ixodes scapularis glutaminyl cyclase with one K ion bound to the active site== | |||
<StructureSection load='7d23' size='340' side='right'caption='[[7d23]], [[Resolution|resolution]] 1.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7d23]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ixodes_scapularis Ixodes scapularis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D23 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D23 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]] 1.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=7d23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d23 OCA], [https://pdbe.org/7d23 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d23 RCSB], [https://www.ebi.ac.uk/pdbsum/7d23 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d23 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/QPCT_IXOSC QPCT_IXOSC] Responsible for the biosynthesis of pyroglutamyl peptides (PubMed:23770496, PubMed:24598748). Seems to have a preference for substrates with neutral or hydrophobic amino-acid residues at the second and third positions (PubMed:24598748). Shows activity towards the peptides [Gln-1]-corazonin, [Gln-1]-periviscerokinin and [Gln-1]-sulfakinin (PubMed:24598748).<ref>PMID:23770496</ref> <ref>PMID:24598748</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Proteins with sequence or structure similar to those of di-Zn exopeptidases are usually classified as the M28-family enzymes, including the mammalian-type glutaminyl cyclases (QCs). QC catalyzes protein N-terminal pyroglutamate formation, a posttranslational modification important under many physiological and pathological conditions, and is a drug target for treating neurodegenerative diseases, cancers and inflammatory disorders. Without functional characterization, mammalian QCs and their orthologs remain indistinguishable at the sequence and structure levels from other M28-family proteins, leading to few reported QCs. Here, we show that a low-barrier carboxylic-acid hydrogen-bond network (CAHBN) is required for QC activity and discriminates QCs from M28-family peptidases. We demonstrate that the CAHBN-containing M28 peptidases deposited in the PDB are indeed QCs. Our analyses identify several thousands of QCs from the three domains of life, and we enzymatically and structurally characterize several. For the first time, the interplay between a CAHBN and the binuclear metal-binding center of mammalian QCs is made clear. We found that the presence or absence of CAHBN is a key discriminator for the formation of either the mono-Zn QCs or the di-Zn exopeptidases. Our study helps explain the possible roles of QCs in life. | |||
A unique carboxylic-acid hydrogen-bond network (CAHBN) confers glutaminyl cyclase activity on M28 family enzymes.,Huang KF, Huang JS, Wu ML, Hsieh WL, Hsu KC, Hsu HL, Ko TP, H-J Wang A J Mol Biol. 2021 Mar 24:166960. doi: 10.1016/j.jmb.2021.166960. PMID:33774034<ref>PMID:33774034</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7d23" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Glutaminyl cyclase|Glutaminyl cyclase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Ixodes scapularis]] | |||
[[Category: Large Structures]] | |||
[[Category: Hsieh W-L]] | |||
[[Category: Huang J-S]] | |||
[[Category: Huang K-F]] | |||
[[Category: Wang AH-J]] | |||
[[Category: Wu M-L]] | |||