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| | <StructureSection load='7d1n' size='340' side='right'caption='[[7d1n]], [[Resolution|resolution]] 2.26Å' scene=''> | | <StructureSection load='7d1n' size='340' side='right'caption='[[7d1n]], [[Resolution|resolution]] 2.26Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7d1n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Black-legged_tick Black-legged tick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D1N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7d1n]] 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=7D1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D1N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</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]] 2.26Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">8042451, IscW_ISCW023264 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6945 Black-legged tick])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene></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=7d1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d1n OCA], [https://pdbe.org/7d1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d1n RCSB], [https://www.ebi.ac.uk/pdbsum/7d1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d1n 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=7d1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d1n OCA], [https://pdbe.org/7d1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d1n RCSB], [https://www.ebi.ac.uk/pdbsum/7d1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d1n ProSAT]</span></td></tr> |
| | </table> | | </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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 7d1n" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 7d1n" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glutaminyl cyclase|Glutaminyl cyclase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Black-legged tick]] | + | [[Category: Ixodes scapularis]] |
| - | [[Category: Glutaminyl-peptide cyclotransferase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hsieh, W L]] | + | [[Category: Hsieh W-L]] |
| - | [[Category: Huang, J S]] | + | [[Category: Huang J-S]] |
| - | [[Category: Huang, K F]] | + | [[Category: Huang K-F]] |
| - | [[Category: Wang, A H.J]] | + | [[Category: Wang AH-J]] |
| - | [[Category: Wu, M L]] | + | [[Category: Wu M-L]] |
| - | [[Category: Glutaminyl cyclase]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
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).[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Adamson SW, Browning RE, Chao CC, Bateman RC Jr, Ching WM, Karim S. Molecular characterization of tick salivary gland glutaminyl cyclase. Insect Biochem Mol Biol. 2013 Sep;43(9):781-93. doi: 10.1016/j.ibmb.2013.05.011. , Epub 2013 Jun 13. PMID:23770496 doi:http://dx.doi.org/10.1016/j.ibmb.2013.05.011
- ↑ Huang KF, Hsu HL, Karim S, Wang AH. Structural and functional analyses of a glutaminyl cyclase from Ixodes scapularis reveal metal-independent catalysis and inhibitor binding. Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):789-801. doi:, 10.1107/S1399004713033488. Epub 2014 Feb 22. PMID:24598748 doi:http://dx.doi.org/10.1107/S1399004713033488
- ↑ Huang KF, Huang JS, Wu ML, Hsieh WL, Hsu KC, Hsu HL, Ko TP, H-J Wang A. A unique carboxylic-acid hydrogen-bond network (CAHBN) confers glutaminyl cyclase activity on M28 family enzymes. J Mol Biol. 2021 Mar 24:166960. doi: 10.1016/j.jmb.2021.166960. PMID:33774034 doi:http://dx.doi.org/10.1016/j.jmb.2021.166960
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