7c3g

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (15:53, 29 November 2023) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 7c3g is ON HOLD until Paper Publication
+
==Crystal structure of human ALK2 kinase domain with R206H mutation in complex with a bicyclic pyrazole inhibitor RK-73134==
 +
<StructureSection load='7c3g' size='340' side='right'caption='[[7c3g]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[7c3g]] 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=7C3G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C3G 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]] 1.802&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FH0:~{N}-[4-(4-methylpiperazin-1-yl)phenyl]-4-(2-pyridin-3-yl-6,7-dihydro-4~{H}-pyrazolo[5,1-c][1,4]oxazin-3-yl)pyrimidin-2-amine'>FH0</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7c3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c3g OCA], [https://pdbe.org/7c3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c3g RCSB], [https://www.ebi.ac.uk/pdbsum/7c3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c3g ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/ACVR1_HUMAN ACVR1_HUMAN] Fibrodysplasia ossificans progressiva. Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:[https://omim.org/entry/135100 135100]. FOP is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification in FOP begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to extra-articular ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible.<ref>PMID:16642017</ref> <ref>PMID:19085907</ref> <ref>PMID:19330033</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/ACVR1_HUMAN ACVR1_HUMAN] On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin. May be involved for left-right pattern formation during embryogenesis (By similarity).
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Mutant activin receptor-like kinase-2 (ALK2) is associated with the pathogenesis of fibrodysplasia ossificans progressiva, making it an attractive target for therapeutic intervention. We synthesized a new series of bicyclic pyrazoles and evaluated their mutant ALK2 enzyme inhibitory activities, leading to the identification of 8 as the most potent inhibitor. This compound showed moderate microsomal metabolic stability and human ether-a-go-go related gene (hERG) safety. In C2C12 cells carrying mutant ALK2 (R206H), 8 efficiently inhibited the bone morphogenetic protein (BMP)-induced alkaline phosphatase activity.
-
Authors:
+
Novel bicyclic pyrazoles as potent ALK2 (R206H) inhibitors for the treatment of fibrodysplasia ossificans progressiva.,Yamamoto H, Sakai N, Ohte S, Sato T, Sekimata K, Matsumoto T, Nakamura K, Watanabe H, Mishima-Tsumagari C, Tanaka A, Hashizume Y, Honma T, Katagiri T, Miyazono K, Tomoda H, Shirouzu M, Koyama H Bioorg Med Chem Lett. 2021 Feb 18;38:127858. doi: 10.1016/j.bmcl.2021.127858. PMID:33609658<ref>PMID:33609658</ref>
-
Description:
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
 +
<div class="pdbe-citations 7c3g" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Matsumoto T]]
 +
[[Category: Mishima-Tsumagari C]]
 +
[[Category: Sakai N]]
 +
[[Category: Shirouzu M]]

Current revision

Crystal structure of human ALK2 kinase domain with R206H mutation in complex with a bicyclic pyrazole inhibitor RK-73134

PDB ID 7c3g

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/7c3g"
Personal tools