1ta2: Difference between revisions

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-[[Image:1ta2.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1ta2", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_1ta2|  PDB=1ta2  |  SCENE=  }}
-'''Crystal structure of thrombin in complex with compound 1'''
+==Crystal structure of thrombin in complex with compound 1==
+<StructureSection load='1ta2' size='340' side='right'caption='[[1ta2]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1ta2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TA2 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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=176:1-(2-AMINO-3,3-DIPHENYL-PROPIONYL)-PYRROLIDINE-3-CARBOXYLIC+ACID+2,5-DICHLORO-BENZYLAMIDE'>176</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</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=1ta2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ta2 OCA], [https://pdbe.org/1ta2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ta2 RCSB], [https://www.ebi.ac.uk/pdbsum/1ta2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ta2 ProSAT]</span></td></tr>
+</table>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ta/1ta2_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ta2 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.
-==Overview==
+Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position.,Tucker TJ, Brady SF, Lumma WC, Lewis SD, Gardell SJ, Naylor-Olsen AM, Yan Y, Sisko JT, Stauffer KJ, Lucas BJ, Lynch JJ, Cook JJ, Stranieri MT, Holahan MA, Lyle EA, Baskin EP, Chen IW, Dancheck KB, Krueger JA, Cooper CM, Vacca JP J Med Chem. 1998 Aug 13;41(17):3210-9. PMID:9703466<ref>PMID:9703466</ref>
-As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-TA2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TA2 OCA].
+</div>
+<div class="pdbe-citations 1ta2" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position., Tucker TJ, Brady SF, Lumma WC, Lewis SD, Gardell SJ, Naylor-Olsen AM, Yan Y, Sisko JT, Stauffer KJ, Lucas BJ, Lynch JJ, Cook JJ, Stranieri MT, Holahan MA, Lyle EA, Baskin EP, Chen IW, Dancheck KB, Krueger JA, Cooper CM, Vacca JP, J Med Chem. 1998 Aug 13;41(17):3210-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9703466 9703466]
+*[[Hirudin 3D structures|Hirudin 3D structures]]
+*[[Thrombin 3D Structures|Thrombin 3D Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Hirudo medicinalis]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Thrombin]]
+[[Category: Baskin EP]]
-[[Category: Baskin, E P.]]
+[[Category: Brady SF]]
-[[Category: Brady, S F.]]
+[[Category: Chen I-W]]
-[[Category: Chen, I W.]]
+[[Category: Cook JJ]]
-[[Category: Cook, J J.]]
+[[Category: Cooper CM]]
-[[Category: Cooper, C M.]]
+[[Category: Dancheck KB]]
-[[Category: Dancheck, K B.]]
+[[Category: Gardel SJ]]
-[[Category: Gardel, S J.]]
+[[Category: Holahan MA]]
-[[Category: Holahan, M A.]]
+[[Category: Krueger JA]]
-[[Category: Krueger, J A.]]
+[[Category: Lewis SD]]
-[[Category: Lewis, S D.]]
+[[Category: Lucas BY]]
-[[Category: Lucas, B Y.]]
+[[Category: Lumma WC]]
-[[Category: Lumma, W C.]]
+[[Category: Lyle EA]]
-[[Category: Lyle, E A.]]
+[[Category: Lynch JJ]]
-[[Category: Lynch, J J.]]
+[[Category: Naylor-Olsen AM]]
-[[Category: Naylor-Olsen, A M.]]
+[[Category: Sisko JT]]
-[[Category: Sisko, J T.]]
+[[Category: Stauffer KJ]]
-[[Category: Stauffer, K J.]]
+[[Category: Stranieri MT]]
-[[Category: Stranieri, M T.]]
+[[Category: Tucker TJ]]
-[[Category: Tucker, T J.]]
+[[Category: Vacca JP]]
-[[Category: Vacca, J P.]]
+[[Category: Yan Y]]
-[[Category: Yan, Y.]]
-[[Category: Thrombin inhibitor complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 09:43:41 2008''