1mue: Difference between revisions

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-{{Seed}}
-[[Image:1mue.png|left|200px]]
-<!--
+==Thrombin-Hirugen-L405,426==
-The line below this paragraph, containing "STRUCTURE_1mue", creates the "Structure Box" on the page.
+<StructureSection load='1mue' size='340' side='right'caption='[[1mue]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1mue]] is a 3 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=1MUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MUE FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</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&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDD:2-(6-CHLORO-3-{[2,2-DIFLUORO-2-(1-OXIDO-2-PYRIDINYL)ETHYL]AMINO}-2-OXO-1(2H)-PYRAZINYL)-N-[(2-FLUOROPHENYL)METHYL]ACETAMIDE'>CDD</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
-{{STRUCTURE_1mue|  PDB=1mue  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mue OCA], [https://pdbe.org/1mue PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mue RCSB], [https://www.ebi.ac.uk/pdbsum/1mue PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mue ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[https://omim.org/entry/613679 613679]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref>   Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref>   Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[https://omim.org/entry/188050 188050]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis.  Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[https://omim.org/entry/614390 614390]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>
+== 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/mu/1mue_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=1mue ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+In this manuscript we demonstrate that a modification principally directed toward the improvement of the aqueous solubility (i.e., introduction a P3 pyridine N-oxide) of the previous lead compound afforded a new series of potent orally bioavailable P1 N-benzylamide thrombin inhibitors. An expedited investigation of the P1 SAR with respect to oral bioavailability, plasma half-life, and human liver microsome stability revealed 5 as the best candidate for advanced evaluation.
-===Thrombin-Hirugen-L405,426===
+Pharmacokinetic optimization of 3-amino-6-chloropyrazinone acetamide thrombin inhibitors. Implementation of P3 pyridine N-oxides to deliver an orally bioavailable series containing P1 N-benzylamides.,Burgey CS, Robinson KA, Lyle TA, Nantermet PG, Selnick HG, Isaacs RC, Lewis SD, Lucas BJ, Krueger JA, Singh R, Miller-Stein C, White RB, Wong B, Lyle EA, Stranieri MT, Cook JJ, McMasters DR, Pellicore JM, Pal S, Wallace AA, Clayton FC, Bohn D, Welsh DC, Lynch JJ Jr, Yan Y, Chen Z, Kuo L, Gardell SJ, Shafer JA, Vacca JP Bioorg Med Chem Lett. 2003 Apr 7;13(7):1353-7. PMID:12657281<ref>PMID:12657281</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1mue" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_12657281}}, adds the Publication Abstract to the page
+*[[Hirudin 3D structures|Hirudin 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 12657281 is the PubMed ID number.
+*[[Thrombin 3D Structures|Thrombin 3D Structures]]
--->
+== References ==
-{{ABSTRACT_PUBMED_12657281}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-MUE is a 3 chains structure of sequences 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=1MUE OCA].
+[[Category: Hirudo medicinalis]]
-==Reference==
-<ref group="xtra">PMID:12657281</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Thrombin]]
+[[Category: Large Structures]]
-[[Category: Bohn, D.]]
+[[Category: Bohn D]]
-[[Category: Burgey, C S.]]
+[[Category: Burgey CS]]
-[[Category: Chen, Z.]]
+[[Category: Chen Z]]
-[[Category: Clayton, F C.]]
+[[Category: Clayton FC]]
-[[Category: Cook, J J.]]
+[[Category: Cook JJ]]
-[[Category: Gardell, S J.]]
+[[Category: Gardell SJ]]
-[[Category: Isaacs, R C.]]
+[[Category: Isaacs RC]]
-[[Category: Krueger, J A.]]
+[[Category: Krueger JA]]
-[[Category: Kuo, L.]]
+[[Category: Kuo L]]
-[[Category: Lewis, S D.]]
+[[Category: Lewis SD]]
-[[Category: Lucas, B J.]]
+[[Category: Lucas BJ]]
-[[Category: Lyle, E A.]]
+[[Category: Lyle EA]]
-[[Category: Lyle, T A.]]
+[[Category: Lyle TA]]
-[[Category: Lynch, J J.]]
+[[Category: Lynch JJ]]
-[[Category: McMasters, D R.]]
+[[Category: McMasters DR]]
-[[Category: Miller-Stein, C.]]
+[[Category: Miller-Stein C]]
-[[Category: Nantermet, P G.]]
+[[Category: Nantermet PG]]
-[[Category: Pal, S.]]
+[[Category: Pal S]]
-[[Category: Pellicore, J M.]]
+[[Category: Pellicore JM]]
-[[Category: Robinson, K A.]]
+[[Category: Robinson KA]]
-[[Category: Selnick, H G.]]
+[[Category: Selnick HG]]
-[[Category: Shafer, J A.]]
+[[Category: Shafer JA]]
-[[Category: Singh, R.]]
+[[Category: Singh R]]
-[[Category: Stranieri, M T.]]
+[[Category: Stranieri MT]]
-[[Category: Vacca, J P.]]
+[[Category: Vacca JP]]
-[[Category: Wallace, A A.]]
+[[Category: Wallace AA]]
-[[Category: Welsh, D C.]]
+[[Category: Welsh DC]]
-[[Category: White, R B.]]
+[[Category: White RB]]
-[[Category: Wong, B.]]
+[[Category: Wong B]]
-[[Category: Yan, Y.]]
+[[Category: Yan Y]]
-[[Category: Alpha thrombin-hirugen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 22:35:30 2009''