View source for 4mhn


==Crystal structure of a glutaminyl cyclase from Ixodes scapularis==
<StructureSection load='4mhn' size='340' side='right'caption='[[4mhn]], [[Resolution|resolution]] 1.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4mhn]] 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=4MHN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MHN 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]] 1.15&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mhn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mhn OCA], [https://pdbe.org/4mhn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mhn RCSB], [https://www.ebi.ac.uk/pdbsum/4mhn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mhn 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 ==
Glutaminyl cyclases (QCs) from mammals and Drosophila are zinc-dependent enzymes that catalyze N-terminal pyroglutamate formation of numerous proteins and peptides. These enzymes have been found to be critical for the oviposition and embryogenesis of ticks, implying that they are possible physiological targets for tick control. Here, 1.10-1.15 A resolution structures of a metal-independent QC from the black-legged tick Ixodes scapularis (Is-QC) are reported. The structures exhibit the typical scaffold of mammalian QCs but have two extra disulfide bridges that stabilize the central beta-sheet, resulting in an increased thermal stability. Is-QC contains ~0.5 stoichiometric zinc ions, which could be removed by 1 mM EDTA. Compared with the Zn-bound form, apo-Is-QC has a nearly identical active-site structure and stability, but unexpectedly possesses significantly increased QC activities towards both synthetic and physiological substrates. Enzyme-kinetic analysis revealed that apo-Is-QC has a stronger substrate-binding affinity, suggesting that bound zinc interferes with substrate binding during catalysis. The structures of Is-QC bound to the inhibitor PBD150 revealed similar binding modes to both forms of Is-QC, with the exception of the inhibitor imidazole ring, which is consistent with the comparable inhibition activities of the inhibitor towards both forms of Is-QC. These findings have implications for the design of new QC inhibitors.

Structural and functional analyses of a glutaminyl cyclase from Ixodes scapularis reveal metal-independent catalysis and inhibitor binding.,Huang KF, Hsu HL, Karim S, Wang AH Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):789-801. doi:, 10.1107/S1399004713033488. Epub 2014 Feb 22. PMID:24598748<ref>PMID:24598748</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4mhn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutaminyl cyclase|Glutaminyl cyclase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Ixodes scapularis]]
[[Category: Large Structures]]
[[Category: Hsu HL]]
[[Category: Huang KF]]
[[Category: Wang AHJ]]