2bmg: Difference between revisions

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-[[Image:2bmg.gif|left|200px]]<br />
-<applet load="2bmg" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2bmg, resolution 2.70&Aring;" />
-'''CRYSTAL STRUCTURE OF FACTOR XA IN COMPLEX WITH 50'''<br />
-==Disease==
+==Crystal structure of factor Xa in complex with 50==
-Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]]
+<StructureSection load='2bmg' size='340' side='right'caption='[[2bmg]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2bmg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BMG 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]] 2.7&#8491;</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=I1H:3-[2-(2,4-DICHLOROPHENYL)ETHOXY]-4-METHOXY-N-[(1-PYRIDIN-4-YLPIPERIDIN-4-YL)METHYL]BENZAMIDE'>I1H</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=2bmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bmg OCA], [https://pdbe.org/2bmg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bmg RCSB], [https://www.ebi.ac.uk/pdbsum/2bmg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bmg ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[https://omim.org/entry/227600 227600]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
+== 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/bm/2bmg_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=2bmg ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The design, synthesis, and structure-activity relationship of 3-oxybenzamides as potent inhibitors of the coagulation protease factor Xa are described on the basis of X-ray structures, privileged structure motifs, and SAR information. A total of six X-ray structures of fXa/inhibitor complexes led us to identify the major protein-ligand interactions. The binding mode is characterized by a lipophilic dichlorophenyl substituent interacting with Tyr228 in the protease S1 pocket, while polar parts are accommodated in S4. This alignment in combination with docking allowed derivation of 3D-QSAR models and tailored scoring functions to rationalize biological affinity and provide guidelines for optimization. The resulting models showed good correlation coefficients and predictions of external test sets. Furthermore, they correspond to binding site topologies in terms of steric, electrostatic, and hydrophobic complementarity. Two approaches to derive tailored scoring functions combining binding site and ligand information led to predictive models with acceptable predictions of the external set. Good correlations to experimental affinities were obtained for both AFMoC (adaptation of fields for molecular comparison) and the novel TScore function. The SAR information from 3D-QSAR and tailored scoring functions agrees with all experimental data and provides guidelines and reasonable activity estimations for novel fXa inhibitors.
-==About this Structure==
+Structural requirements for factor Xa inhibition by 3-oxybenzamides with neutral P1 substituents: combining X-ray crystallography, 3D-QSAR, and tailored scoring functions.,Matter H, Will DW, Nazare M, Schreuder H, Laux V, Wehner V J Med Chem. 2005 May 5;48(9):3290-312. PMID:15857135<ref>PMID:15857135</ref>
-BMG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and I1H as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BMG OCA].
-[[Category: Coagulation factor Xa]]
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2bmg" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Factor Xa|Factor Xa]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Laux, V.]]
+[[Category: Laux V]]
-[[Category: Liesum, A.]]
+[[Category: Liesum A]]
-[[Category: Loenze, P.]]
+[[Category: Loenze P]]
-[[Category: Matter, H.]]
+[[Category: Matter H]]
-[[Category: Nazare, M.]]
+[[Category: Nazare M]]
-[[Category: Schreuder, H.]]
+[[Category: Schreuder H]]
-[[Category: Wehner, V.]]
+[[Category: Wehner V]]
-[[Category: Will, D.W.]]
+[[Category: Will DW]]
-[[Category: CA]]
-[[Category: I1H]]
-[[Category: blood coagulation factor]]
-[[Category: drug design]]
-[[Category: hydrolase]]
-[[Category: protein inhibitor complex]]
-[[Category: serine proteinase]]
-[[Category: thrombosis]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:04:08 2007''