|
|
(2 intermediate revisions not shown.) |
Line 3: |
Line 3: |
| <StructureSection load='1lqe' size='340' side='right'caption='[[1lqe]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='1lqe' size='340' side='right'caption='[[1lqe]], [[Resolution|resolution]] 2.20Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[1lqe]] 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=1LQE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LQE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1lqe]] 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=1LQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LQE FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IMA:[4-({[5-BENZYLOXY-1-(3-CARBAMIMIDOYL-BENZYL)-1H-INDOLE-2-CARBONYL]-AMINO}-METHYL)-PHENYL]-TRIMETHYL-AMMONIUM'>IMA</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]] 2.2Å</td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lpg|1lpg]], [[1lpk|1lpk]], [[1lpz|1lpz]], [[1lqd|1lqd]]</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=IMA:[4-({[5-BENZYLOXY-1-(3-CARBAMIMIDOYL-BENZYL)-1H-INDOLE-2-CARBONYL]-AMINO}-METHYL)-PHENYL]-TRIMETHYL-AMMONIUM'>IMA</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=1lqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lqe OCA], [https://pdbe.org/1lqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lqe RCSB], [https://www.ebi.ac.uk/pdbsum/1lqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lqe ProSAT]</span></td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lqe OCA], [http://pdbe.org/1lqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lqe RCSB], [http://www.ebi.ac.uk/pdbsum/1lqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lqe 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]] |
Line 14: |
Line 15: |
| <jmolCheckbox> | | <jmolCheckbox> |
| <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lq/1lqe_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lq/1lqe_consurf.spt"</scriptWhenChecked> |
- | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| </jmolCheckbox> | | </jmolCheckbox> |
Line 30: |
Line 31: |
| | | |
| ==See Also== | | ==See Also== |
- | *[[Trypsin|Trypsin]] | + | *[[Trypsin 3D structures|Trypsin 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
Line 37: |
Line 38: |
| [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Trypsin]]
| + | [[Category: Liesum A]] |
- | [[Category: Liesum, A]] | + | [[Category: Schreuder HA]] |
- | [[Category: Schreuder, H A]] | + | |
- | [[Category: Blood coagulation factor]]
| + | |
- | [[Category: Enzyme-inhibitor complex]]
| + | |
- | [[Category: Factor xa inhibitor]]
| + | |
- | [[Category: Hydrolase]]
| + | |
- | [[Category: Serine proteinase]]
| + | |
| 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
A series of 138 nonchiral 3-amidinobenzyl-1H-indole-2-carboxamides and analogues as inhibitors of the blood coagulation enzyme factor Xa (fXa) were designed, synthesized, and investigated by X-ray structure analysis and 3D quantitative structure-activity relationship (QSAR) studies (CoMFA, CoMSIA) in order to identify important protein-ligand interactions responsible for biological affinity and selectivity. Several compounds from this series are highly potent and selective inhibitors of this important enzyme linking extrinsic and intrinsic coagulation pathways. To rationalize biological affinity and to provide guidelines for further design, all compounds were docked into the factor Xa binding site. Those docking studies were based on X-ray structures of factor Xa in complex with literature-known inhibitors. It was possible to validate those binding modes by four X-ray crystal structures of representative ligands in factor Xa, while one ligand was additionally crystallized in trypsin to rationalize requirements for selective factor Xa inhibition. The 3D-QSAR models based on a superposition rule derived from these docking studies were validated using conventional and cross-validated r(2) values using the leave-one-out method and repeated analyses using two randomly chosen cross-validation groups plus randomization of biological activities. This led to consistent and highly predictive 3D-QSAR models with good correlation coefficients for both CoMFA and CoMSIA, which were found to correspond to experimentally determined factor Xa binding site topology in terms of steric, electrostatic, and hydrophobic complementarity. Subsets selected as smaller training sets using 2D fingerprints and maximum dissimilarity methods resulted in 3D-QSAR models with remarkable correlation coefficients and a high predictive power. The final quantitative SAR information agrees with all experimental data for the binding topology and thus provides reasonable activity predictions for novel factor Xa inhibitors.
Design and quantitative structure-activity relationship of 3-amidinobenzyl-1H-indole-2-carboxamides as potent, nonchiral, and selective inhibitors of blood coagulation factor Xa.,Matter H, Defossa E, Heinelt U, Blohm PM, Schneider D, Muller A, Herok S, Schreuder H, Liesum A, Brachvogel V, Lonze P, Walser A, Al-Obeidi F, Wildgoose P J Med Chem. 2002 Jun 20;45(13):2749-69. PMID:12061878[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Matter H, Defossa E, Heinelt U, Blohm PM, Schneider D, Muller A, Herok S, Schreuder H, Liesum A, Brachvogel V, Lonze P, Walser A, Al-Obeidi F, Wildgoose P. Design and quantitative structure-activity relationship of 3-amidinobenzyl-1H-indole-2-carboxamides as potent, nonchiral, and selective inhibitors of blood coagulation factor Xa. J Med Chem. 2002 Jun 20;45(13):2749-69. PMID:12061878
|