3ens

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (01:46, 21 November 2024) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:3ens.jpg|left|200px]]
 
-
<!--
+
==Crystal structure of human FXA in complex with methyl (2Z)-3-[(3-chloro-1H-indol-7-yl)amino]-2-cyano-3-{[(3S)-2-oxo-1-(2-oxo-2-pyrrolidin-1-ylethyl)azepan-3-yl]amino}acrylate==
-
The line below this paragraph, containing "STRUCTURE_3ens", creates the "Structure Box" on the page.
+
<StructureSection load='3ens' size='340' side='right'caption='[[3ens]], [[Resolution|resolution]] 2.30&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'>[[3ens]] is a 4 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=3ENS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ENS 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]] 2.3&#8491;</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=ENS:METHYL+(2Z)-3-[(3-CHLORO-1H-INDOL-7-YL)AMINO]-2-CYANO-3-{[(3S)-2-OXO-1-(2-OXO-2-PYRROLIDIN-1-YLETHYL)AZEPAN-3-YL]AMINO}ACRYLATE'>ENS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-
{{STRUCTURE_3ens| PDB=3ens | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ens FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ens OCA], [https://pdbe.org/3ens PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ens RCSB], [https://www.ebi.ac.uk/pdbsum/3ens PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ens 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/en/3ens_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=3ens ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
An indole-based P1 moiety was incorporated into a previously established factor Xa inhibitor series. The indole group was designed to hydrogen-bond with the carbonyl of Gly218, while its 3-methyl or 3-chloro substituent was intended to interact with Tyr228. These interactions were subsequently observed in the X-ray crystal structure of compound 18. SAR studies led to the identification of compound 20 as the most potent FXa inhibitor in this series (IC 50 = 2.4 nM, EC 2xPT = 1.2 muM). An in-depth energetic analysis suggests that the increased binding energy of 3-chloroindole-versus 3-methylindole-containing compounds in this series is due primarily to (a) the more hydrophobic nature of chloro- versus methyl-containing compounds and (b) an increased interaction of 3-chloroindole versus 3-methylindole with Gly218 backbone. The stronger hydrophobicity of chloro- versus methyl-substituted aromatics may partly explain the general preference for chloro- versus methyl-substituted P1 groups in FXa, which extends beyond the current series.
-
===Crystal structure of human FXA in complex with methyl (2Z)-3-[(3-chloro-1H-indol-7-yl)amino]-2-cyano-3-{[(3S)-2-oxo-1-(2-oxo-2-pyrrolidin-1-ylethyl)azepan-3-yl]amino}acrylate===
+
Design, Structure-Activity Relationships, X-ray Crystal Structure, and Energetic Contributions of a Critical P1 Pharmacophore: 3-Chloroindole-7-yl-Based Factor Xa Inhibitors.,Shi Y, Sitkoff D, Zhang J, Klei HE, Kish K, Liu EC, Hartl KS, Seiler SM, Chang M, Huang C, Youssef S, Steinbacher TE, Schumacher WA, Grazier N, Pudzianowski A, Apedo A, Discenza L, Yanchunas J Jr, Stein PD, Atwal KS J Med Chem. 2008 Nov 11. PMID:18998662<ref>PMID:18998662</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 3ens" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_18998662}}, adds the Publication Abstract to the page
+
*[[Factor Xa|Factor Xa]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 18998662 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_18998662}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
-
3ENS is a 4 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=3ENS OCA].
+
-
 
+
-
==Reference==
+
-
Design, Structure-Activity Relationships, X-ray Crystal Structure, and Energetic Contributions of a Critical P1 Pharmacophore: 3-Chloroindole-7-yl-Based Factor Xa Inhibitors., Shi Y, Sitkoff D, Zhang J, Klei HE, Kish K, Liu EC, Hartl KS, Seiler SM, Chang M, Huang C, Youssef S, Steinbacher TE, Schumacher WA, Grazier N, Pudzianowski A, Apedo A, Discenza L, Yanchunas J Jr, Stein PD, Atwal KS, J Med Chem. 2008 Nov 11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18998662 18998662]
+
-
[[Category: Coagulation factor Xa]]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Klei, H E.]]
+
[[Category: Large Structures]]
-
[[Category: Blood clotting]]
+
[[Category: Klei HE]]
-
[[Category: Blood coagulation factor]]
+
-
[[Category: Calcium]]
+
-
[[Category: Cleavage on pair of basic residue]]
+
-
[[Category: Egf-like domain]]
+
-
[[Category: Epidermal growth factor like domain]]
+
-
[[Category: Gamma-carboxyglutamic acid]]
+
-
[[Category: Glycoprotein]]
+
-
[[Category: Hydrolase]]
+
-
[[Category: Hydroxylation]]
+
-
[[Category: Polymorphism]]
+
-
[[Category: Serine protease]]
+
-
[[Category: Zymogen]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 31 10:33:40 2008''
+

Current revision

Crystal structure of human FXA in complex with methyl (2Z)-3-[(3-chloro-1H-indol-7-yl)amino]-2-cyano-3-{[(3S)-2-oxo-1-(2-oxo-2-pyrrolidin-1-ylethyl)azepan-3-yl]amino}acrylate

PDB ID 3ens

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ens"
Personal tools