View source for 4gux


==Crystal structure of trypsin:MCoTi-II complex==
<StructureSection load='4gux' size='340' side='right'caption='[[4gux]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gux]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Momordica_cochinchinensis Momordica cochinchinensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GUX 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]] 1.803&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=4gux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gux OCA], [https://pdbe.org/4gux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gux RCSB], [https://www.ebi.ac.uk/pdbsum/4gux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gux ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MCoTI-II is a head-to-tail cyclic peptide with potent trypsin inhibitory activity and, on the basis of its exceptional proteolytic stability, is a valuable template for the design of novel drug leads. Insights into inhibitor dynamics and interactions with biological targets are critical for drug design studies, particularly for protease targets. Here, we show that the cyclization and active site loops of MCoTI-II are flexible in solution, but when bound to trypsin, the active site loop converges to a single well defined conformation. This finding of reduced flexibility on binding is in contrast to a recent study on the homologous peptide MCoTI-I, which suggested that regions of the peptide are more flexible upon binding to trypsin. We provide a possible explanation for this discrepancy based on degradation of the complex over time. Our study also unexpectedly shows that the cyclization loop, not present in acyclic homologues, facilitates potent trypsin inhibitory activity by engaging in direct binding interactions with trypsin.

Structural insights into the role of the cyclic backbone in a squash trypsin inhibitor.,Daly NL, Thorstholm L, Greenwood KP, King GJ, Rosengren KJ, Heras B, Martin JL, Craik DJ J Biol Chem. 2013 Dec 13;288(50):36141-8. doi: 10.1074/jbc.M113.528240. Epub 2013, Oct 29. PMID:24169696<ref>PMID:24169696</ref>

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

==See Also==
*[[Trypsin 3D structures|Trypsin 3D structures]]
*[[Trypsin inhibitor 3D structures|Trypsin inhibitor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Momordica cochinchinensis]]
[[Category: Craik DJ]]
[[Category: Daly NL]]
[[Category: Greenwood KP]]
[[Category: Heras B]]
[[Category: King GJ]]
[[Category: Martin JL]]
[[Category: Rosengren KJ]]
[[Category: Thorstholm L]]