|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='5eg4' size='340' side='right'caption='[[5eg4]], [[Resolution|resolution]] 1.32Å' scene=''> | | <StructureSection load='5eg4' size='340' side='right'caption='[[5eg4]], [[Resolution|resolution]] 1.32Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5eg4]] 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=5EG4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EG4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5eg4]] 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=5EG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EG4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5N7:(13S,16R)-N-(4-CARBAMIMIDOYLBENZYL)-16-((N-CYCLOHEXYLSULFAMOYL)AMINO)-3,9,15-TRIOXO-2,10,14-TRIAZA-6(1,4)-PIPERAZINA-1,11(1,4)-DIBENZENACYCLOHEPTADECAPHANE-13-CARBOXAMIDE'>5N7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.32Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mtb|4mtb]]</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5eg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eg4 OCA], [https://pdbe.org/5eg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eg4 RCSB], [https://www.ebi.ac.uk/pdbsum/5eg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eg4 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=5eg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eg4 OCA], [http://pdbe.org/5eg4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eg4 RCSB], [http://www.ebi.ac.uk/pdbsum/5eg4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eg4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 28: |
| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Trypsin]]
| + | [[Category: Heine A]] |
| - | [[Category: Heine, A]] | + | [[Category: Klebe G]] |
| - | [[Category: Klebe, G]] | + | [[Category: Knoerlein A]] |
| - | [[Category: Knoerlein, A]] | + | [[Category: Steinmetzer T]] |
| - | [[Category: Steinmetzer, T]] | + | [[Category: Wagner S]] |
| - | [[Category: Wagner, S]] | + | |
| - | [[Category: Digestion]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| Structural highlights
Function
TRY1_BOVIN
Publication Abstract from PubMed
New macrocyclic plasmin inhibitors based on our previously optimized P2-P3 core segment have been developed. In the first series, the P4 residue was modified, whereas the 4-amidinobenzylamide in P1 position was maintained. The originally used P4 benzylsulfonyl residue could be replaced by various sulfonyl- or urethane-like protecting groups. In the second series, the P1 benzamidine was modified and a strong potency and excellent selectivity was retained by incorporation of p-xylenediamine. Several analogues inhibit plasmin in the subnanomolar range, and their potency against related trypsin-like serine proteases including trypsin itself could be further reduced. Selected derivatives have been tested in a plasma fibrinolysis assay and are more effective than the reference inhibitor aprotinin. The crystal structure of one inhibitor was determined in complex with trypsin. The binding mode reveals a sterical clash of the inhibitor's linker segment with the 99-hairpin loop of trypsin, which is absent in plasmin.
Optimization of Cyclic Plasmin Inhibitors: From Benzamidines to Benzylamines.,Hinkes S, Wuttke A, Saupe SM, Ivanova T, Wagner S, Knorlein A, Heine A, Klebe G, Steinmetzer T J Med Chem. 2016 Jun 17. PMID:27280436[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hinkes S, Wuttke A, Saupe SM, Ivanova T, Wagner S, Knorlein A, Heine A, Klebe G, Steinmetzer T. Optimization of Cyclic Plasmin Inhibitors: From Benzamidines to Benzylamines. J Med Chem. 2016 Jun 17. PMID:27280436 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00606
|
