7d2b: Difference between revisions
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==Crystal structure of Ixodes scapularis glutaminyl cyclase with a Ni ion bound to the active site== | ==Crystal structure of Ixodes scapularis glutaminyl cyclase with a Ni ion bound to the active site== | ||
<StructureSection load='7d2b' size='340' side='right'caption='[[7d2b]]' scene=''> | <StructureSection load='7d2b' size='340' side='right'caption='[[7d2b]], [[Resolution|resolution]] 1.99Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D2B FirstGlance]. <br> | <table><tr><td colspan='2'>[[7d2b]] 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=7D2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D2B FirstGlance]. <br> | ||
</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=7d2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d2b OCA], [https://pdbe.org/7d2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d2b RCSB], [https://www.ebi.ac.uk/pdbsum/7d2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d2b ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></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='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=7d2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d2b OCA], [https://pdbe.org/7d2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d2b RCSB], [https://www.ebi.ac.uk/pdbsum/7d2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d2b ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<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> | |||
</div> | |||
<div class="pdbe-citations 7d2b" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Black-legged tick]] | |||
[[Category: Glutaminyl-peptide cyclotransferase]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hsieh W | [[Category: Hsieh, W L]] | ||
[[Category: Huang J | [[Category: Huang, J S]] | ||
[[Category: Huang K | [[Category: Huang, K F]] | ||
[[Category: Wang | [[Category: Wang, A H.J]] | ||
[[Category: Wu M | [[Category: Wu, M L]] | ||
[[Category: Glutaminyl cyclase]] | |||
[[Category: Metal binding protein]] | |||
[[Category: Transferase]] | |||
Revision as of 12:11, 5 May 2021
Crystal structure of Ixodes scapularis glutaminyl cyclase with a Ni ion bound to the active siteCrystal structure of Ixodes scapularis glutaminyl cyclase with a Ni ion bound to the active site
Structural highlights
Publication Abstract from PubMedProteins 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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