7d1d: Difference between revisions
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==Crystal structure of Bacteroides thetaiotaomicron glutaminyl cyclase bound to 1-benzylimidazole== | |||
<StructureSection load='7d1d' size='340' side='right'caption='[[7d1d]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7d1d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D1D 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]] 1.75Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BN:1-BENZYL-1H-IMIDAZOLE'>1BN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7d1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d1d OCA], [https://pdbe.org/7d1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d1d RCSB], [https://www.ebi.ac.uk/pdbsum/7d1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d1d ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8A4P9_BACTN Q8A4P9_BACTN] | |||
<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 7d1d" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Glutaminyl cyclase|Glutaminyl cyclase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bacteroides thetaiotaomicron]] | |||
[[Category: Large Structures]] | |||
[[Category: Hsieh W-L]] | |||
[[Category: Huang J-S]] | |||
[[Category: Huang K-F]] | |||
[[Category: Wang AH-J]] | |||
[[Category: Wu M-L]] | |||
Latest revision as of 19:22, 29 November 2023
Crystal structure of Bacteroides thetaiotaomicron glutaminyl cyclase bound to 1-benzylimidazoleCrystal structure of Bacteroides thetaiotaomicron glutaminyl cyclase bound to 1-benzylimidazole
Structural highlights
FunctionPublication 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. See AlsoReferences
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