View source for 4hgc


==Crystal structure of bovine trypsin complexed with sfti-1 analog containing a peptoid residue at position p1==
<StructureSection load='4hgc' size='340' side='right'caption='[[4hgc]], [[Resolution|resolution]] 1.29&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hgc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Helianthus_annuus Helianthus annuus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HGC 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]] 1.29&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NLY:N-(4-AMINOBUTYL)GLYCINE'>NLY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4hgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgc OCA], [https://pdbe.org/4hgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hgc RCSB], [https://www.ebi.ac.uk/pdbsum/4hgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hgc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Peptide-peptoid hybrids are found to be potent inhibitors of serine proteases. These engineered peptidomimetics benefit from both types of units of the biopolymeric structure: the natural inhibitor part serves as a good binding template, while the P1-positioned peptoid component provides complete resistance towards proteolysis. In this report, the mechanism of proteolytic resistance of a P1 peptoid-containing analogue is postulated based on the crystal structure of the (NLys)(5)-modified sunflower trypsin inhibitor SFTI-1 in complex with bovine trypsin solved at 1.29 A resolution. The structural differences between the (NLys)(5)SFTI-1-trypsin complex and the native SFTI-1-trypsin complex are surprisingly small and reveal the key role of the carbonyl group of the Ser214 residue of the enzyme, which is crucial for binding of the inhibitor and plays a crucial role in proteolysis mediated by serine proteases. The incorporated NLys5 peptoid residue prevents Ser214 from forming a hydrogen bond to the P1 residue, and in turn Gln192 does not form a hydrogen bond to the carbonyl group of the P2 residue. It also increases the distance between the Ser214 carbonyl group and the Ser195 residue, thus preventing proteolysis. The hybrid inhibitor structure reported here provides insight into protein-protein interaction, which can be efficiently and selectively probed with the use of peptoids incorporated within endogenous peptide ligands.

Structure of a proteolytically resistant analogue of (NLys)(5)SFTI-1 in complex with trypsin: evidence for the direct participation of the Ser214 carbonyl group in serine protease-mediated proteolysis.,Krzywda S, Jaskolski M, Rolka K, Stawikowski MJ Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):668-75. doi:, 10.1107/S1399004713032252. Epub 2014 Feb 15. PMID:24598736<ref>PMID:24598736</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4hgc" 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: Helianthus annuus]]
[[Category: Large Structures]]
[[Category: Jaskolski M]]
[[Category: Krzywda S]]
[[Category: Rolka K]]
[[Category: Stawikowski M]]