4zae

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
'''Unreleased structure'''
+
==Development of a novel class of potent and selective FIXa inhibitors==
 +
<StructureSection load='4zae' size='340' side='right' caption='[[4zae]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4zae]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZAE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZAE FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4M1:2,6-DICHLORO-N-[(2R)-2-(5,6-DIMETHYL-1H-BENZIMIDAZOL-2-YL)-2-PHENYLETHYL]-4-(4H-1,2,4-TRIAZOL-4-YL)BENZAMIDE'>4M1</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></td></tr>
 +
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_IXa Coagulation factor IXa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.22 3.4.21.22] </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=4zae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zae OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zae RCSB], [http://www.ebi.ac.uk/pdbsum/4zae PDBsum]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[[http://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN]] Defects in F9 are the cause of recessive X-linked hemophilia B (HEMB) [MIM:[http://omim.org/entry/306900 306900]]; also known as Christmas disease.<ref>PMID:8295821</ref> <ref>PMID:2592373</ref> <ref>PMID:2743975</ref> <ref>PMID:6603618</ref> <ref>PMID:3009023</ref> <ref>PMID:3790720</ref> <ref>PMID:3401602</ref> <ref>PMID:3243764</ref> <ref>PMID:2713493</ref> <ref>PMID:2714791</ref> <ref>PMID:2773937</ref> <ref>PMID:2775660</ref> <ref>PMID:2753873</ref> <ref>PMID:2738071</ref> <ref>PMID:2472424</ref> <ref>PMID:2339358</ref> <ref>PMID:2372509</ref> <ref>PMID:2162822</ref> <ref>PMID:1958666</ref> <ref>PMID:1902289</ref> <ref>PMID:1346975</ref> <ref>PMID:1615485</ref> <ref>PMID:8257988</ref> <ref>PMID:8076946</ref> <ref>PMID:8199596</ref> <ref>PMID:7981722</ref> <ref>PMID:8680410</ref> <ref>PMID:9222764</ref> <ref>PMID:9590153</ref> <ref>PMID:9452115</ref> <ref>PMID:9600455</ref> <ref>PMID:10698280</ref> <ref>PMID:10094553</ref> <ref>PMID:11122099</ref> <ref>PMID:12588353</ref> <ref>PMID:12604421</ref> Note=Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide, mutation in position 93 (Alabama) probably fails to bind to cell membranes, mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya OR Hilo) prevent cleavage of the activation peptide. Defects in F9 are the cause of thrombophilia due to factor IX defect (THPH8) [MIM:[http://omim.org/entry/300807 300807]]. A hemostatic disorder characterized by a tendency to thrombosis.<ref>PMID:19846852</ref>
 +
== Function ==
 +
[[http://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN]] Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Using structure based drug design (SBDD), a novel class of potent coagulation Factor IXa (FIXa) inhibitors was designed and synthesized. High selectivity over FXa inhibition was achieved. Selected compounds demonstrated oral bioavailability in rat IV/PO pharmacokinetic (PK) studies. Finally, the pharmacodynamics (PD) of this class of molecules was evaluated in Thrombin Generation Assay (TGA) in Corn Trypsin Inhibitor (CTI) citrated human plasma and demonstrated characteristics of a FIXa inhibitor.
-
The entry 4zae is ON HOLD until Paper Publication
+
Development of a novel class of potent and selective FIXa inhibitors.,Zhang T, Andre P, Bateman TJ, Chen YH, Desai K, Ellsworth K, Geissler WM, Guo L, Hruza A, Jian T, Meng D, Parker DL Jr, Qian X, Reichert P, Sherer EC, Shu M, Smith CJ, Sonatore LM, Tschirret-Guth R, Nolting AF, Orr R, Campeau LC, Araki K, Nishimura T, Sakurada I, Wood HB Bioorg Med Chem Lett. 2015 Apr 29. pii: S0960-894X(15)00389-3. doi:, 10.1016/j.bmcl.2015.04.057. PMID:25978966<ref>PMID:25978966</ref>
-
Authors: Hruza, A., Reichert, P.
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
Description: Development of a novel class of potent and selective FIXa inhibitors
+
== References ==
-
[[Category: Unreleased Structures]]
+
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Coagulation factor IXa]]
[[Category: Hruza, A]]
[[Category: Hruza, A]]
[[Category: Reichert, P]]
[[Category: Reichert, P]]
 +
[[Category: Blood coagulation]]
 +
[[Category: Coagulation factor]]
 +
[[Category: Hydrolase-hydrolase inhibitor complex]]
 +
[[Category: Serine proteinase]]

Revision as of 12:36, 3 June 2015

Development of a novel class of potent and selective FIXa inhibitors

4zae, resolution 1.86Å

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/4zae"
Personal tools