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| | <StructureSection load='1c2e' size='340' side='right'caption='[[1c2e]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='1c2e' size='340' side='right'caption='[[1c2e]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1c2e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C2E OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1C2E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1c2e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C2E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C2E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BAK:BIS(5-AMIDINO-2-BENZIMIDAZOLYL)METHANE+KETONE'>BAK</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 1.65Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c2d|1c2d]], [[1c2f|1c2f]], [[1c2g|1c2g]], [[1c2h|1c2h]], [[1c2i|1c2i]], [[1c2l|1c2l]], [[1c2m|1c2m]], [[1c1n|1c1n]], [[1c1o|1c1o]], [[1c1p|1c1p]], [[1c1q|1c1q]], [[1c1r|1c1r]], [[1c1s|1c1s]], [[1c1t|1c1t]], [[1c1u|1c1u]], [[1c1v|1c1v]], [[1c1w|1c1w]], [[1c2j|1c2j]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BAK:BIS(5-AMIDINO-2-BENZIMIDAZOLYL)METHANE+KETONE'>BAK</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </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=1c2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2e OCA], [https://pdbe.org/1c2e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c2e RCSB], [https://www.ebi.ac.uk/pdbsum/1c2e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c2e ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1c2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2e OCA], [http://pdbe.org/1c2e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c2e RCSB], [http://www.ebi.ac.uk/pdbsum/1c2e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1c2e ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Trypsin]]
| + | [[Category: Katz BA]] |
| - | [[Category: Katz, B A]] | + | [[Category: Luong C]] |
| - | [[Category: Luong, C]] | + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Ph dependence]]
| + | |
| - | [[Category: Serine protease/inhibitor]]
| + | |
| Structural highlights
Function
TRY1_BOVIN
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Many serine proteases are targets for therapeutic intervention because they often play key roles in disease. Small molecule inhibitors of serine proteases with high affinity are especially interesting as they could be used as scaffolds from which to develop drugs selective for protease targets. One such inhibitor is bis(5-amidino-2-benzimidazolyl)methane (BABIM), standing out as the best inhibitor of trypsin (by a factor of over 100) in a series of over 60 relatively closely related analogues. By probing the structural basis of inhibition, we discovered, using crystallographic methods, a new mode of high-affinity binding in which a Zn2+ ion is tetrahedrally coordinated between two chelating nitrogens of BABIM and two active site residues, His57 and Ser 195. Zn2+, at subphysiological levels, enhances inhibition by over 10(3)-fold. The distinct Zn2+ coordination geometry implies a strong dependence of affinity on substituents. This unique structural paradigm has enabled development of potent, highly selective, Zn2+-dependent inhibitors of several therapeutically important serine proteases, using a physiologically ubiquitous metal ion.
Design of potent selective zinc-mediated serine protease inhibitors.,Katz BA, Clark JM, Finer-Moore JS, Jenkins TE, Johnson CR, Ross MJ, Luong C, Moore WR, Stroud RM Nature. 1998 Feb 5;391(6667):608-12. PMID:9468142[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Katz BA, Clark JM, Finer-Moore JS, Jenkins TE, Johnson CR, Ross MJ, Luong C, Moore WR, Stroud RM. Design of potent selective zinc-mediated serine protease inhibitors. Nature. 1998 Feb 5;391(6667):608-12. PMID:9468142 doi:http://dx.doi.org/10.1038/35422
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