7jwx
From Proteopedia
(Difference between revisions)
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<StructureSection load='7jwx' size='340' side='right'caption='[[7jwx]], [[Resolution|resolution]] 2.38Å' scene=''> | <StructureSection load='7jwx' size='340' side='right'caption='[[7jwx]], [[Resolution|resolution]] 2.38Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JWX 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]] 2.38Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38Å</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VN1:4-[(1-{(1S,2S)-1-[1-(4-aminobutyl)-1H-1,2,3-triazol-4-yl]-2-methylbutyl}-1H-1,2,3-triazol-4-yl)methoxy]-3-methoxybenzene-1-carboximidamide'>VN1</scene></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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VN1:4-[(1-{(1S,2S)-1-[1-(4-aminobutyl)-1H-1,2,3-triazol-4-yl]-2-methylbutyl}-1H-1,2,3-triazol-4-yl)methoxy]-3-methoxybenzene-1-carboximidamide'>VN1</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=7jwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jwx OCA], [https://pdbe.org/7jwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jwx RCSB], [https://www.ebi.ac.uk/pdbsum/7jwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jwx ProSAT]</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=7jwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jwx OCA], [https://pdbe.org/7jwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jwx RCSB], [https://www.ebi.ac.uk/pdbsum/7jwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jwx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Function == | ||
| - | [https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Examination of a series of naturally-occurring trypsin inhibitor proteins, led to identification of a set of three residues (which we call the "interface triplet") to be determinant of trypsin binding affinity, hence excellent templates for small molecule mimicry. Consequently, we attempted to use the Exploring Key Orientation (EKO) strategy developed in our lab to evaluate small molecules that mimic the interface triplet regions of natural trypsin inhibitors, and hence potentially might bind and inhibit the catalytic activity of trypsin. A bis-triazole scaffold ("TT-mer") was the most promising of the molecules evaluated in silico. Twelve such compounds were synthesized and assayed against trypsin, among which the best showed a Kd of 2.1 muM. X-ray crystallography revealed a high degree of matching between an illustrative TT-mer's actual binding mode and that of the mimics that overlaid the interface triplet in the crystal structure. Deviation of the third side chain from the PPI structure seems to be due to alleviation of an unfavorable dipole-dipole interaction in the small molecule's actual bound conformation. | ||
| - | |||
| - | Small molecule peptidomimetic trypsin inhibitors: validation of an EKO binding mode, but with a twist.,Lyu RL, Joy S, Packianathan C, Laganowsky A, Burgess K Org Biomol Chem. 2022 Mar 9;20(10):2075-2080. doi: 10.1039/d1ob02127c. PMID:35225309<ref>PMID:35225309</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 7jwx" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Trypsin 3D structures|Trypsin 3D structures]] | *[[Trypsin 3D structures|Trypsin 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Bos taurus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Laganowsky A]] | [[Category: Laganowsky A]] | ||
[[Category: Packianathan C]] | [[Category: Packianathan C]] | ||
Current revision
Crystal Structure of Trypsin Bound O-methyl Benzamidine
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