3q4u - Revision history

OCA at 11:33, 14 March 2024

OCA — Thu, 14 Mar 2024 11:33:36 GMT

←Older revision		Revision as of 11:33, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3q4u' size='340' side='right'caption='[[3q4u]], [[Resolution\|resolution]] 1.82Å' scene=''>		<StructureSection load='3q4u' size='340' side='right'caption='[[3q4u]], [[Resolution\|resolution]] 1.82Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3q4u]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q4U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3q4u]] 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=3Q4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q4U FirstGlance]. <br>
-	</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=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LDN:4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE'>LDN</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.82Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3mtf\|3mtf]], [[3oom\|3oom]]</div></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=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LDN:4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE'>LDN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACVR1, ACVRLK2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></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=3q4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4u OCA], [https://pdbe.org/3q4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q4u RCSB], [https://www.ebi.ac.uk/pdbsum/3q4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q4u ProSAT]</span></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=3q4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4u OCA], [https://pdbe.org/3q4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q4u RCSB], [https://www.ebi.ac.uk/pdbsum/3q4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q4u ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>	+	[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 ==		== 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).	+	[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 ==~~	+
-	Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP). Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-beta signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with K02288 and LDN-193189 revealed additional contacts in the K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development.	+
-		+
-	A new class of small molecule inhibitor of BMP signaling.,Sanvitale CE, Kerr G, Chaikuad A, Ramel MC, Mohedas AH, Reichert S, Wang Y, Triffitt JT, Cuny GD, Yu PB, Hill CS, Bullock AN PLoS One. 2013 Apr 30;8(4):e62721. doi: 10.1371/journal.pone.0062721. Print 2013. PMID:23646137<ref>PMID:23646137</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3q4u" style="background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein serine/threonine kinase]]~~	+	[[Category: Alfano I]]
-	[[Category: Alfano, I]]	+	[[Category: Allerston CK]]
-	[[Category: Allerston~~, C K~~]]	+	[[Category: Arrowsmith CH]]
-	[[Category: Arrowsmith~~, C H~~]]	+	[[Category: Bountra C]]
-	[[Category: Bountra, C]]	+	[[Category: Bullock A]]
-	[[Category: Bullock, A]]	+	[[Category: Chaikuad A]]
-	[[Category: Chaikuad, A]]	+	[[Category: Cooper CDO]]
-	[[Category: Cooper~~, C D.O~~]]	+	[[Category: Daga N]]
-	[[Category: Daga, N]]	+	[[Category: Edwards AM]]
-	~~[[Category: Delft, F von~~]]	+	[[Category: Fedorov O]]
-	[[Category: Edwards~~, A M~~]]	+	[[Category: Gileadi O]]
-	[[Category: Fedorov, O]]	+	[[Category: Krojer T]]
-	[[Category: Gileadi, O]]	+	[[Category: Mahajan P]]
-	[[Category: Krojer, T]]	+	[[Category: Petrie K]]
-	[[Category: Mahajan, P]]	+	[[Category: Sanvitale C]]
-	[[Category: Petrie, K]]	+	[[Category: Vollmar M]]
-	~~[[Category: Structural genomic~~]]	+	[[Category: Weigelt J]]
-	[[Category: Sanvitale, C]]	+	[[Category: Von Delft F]]
-	[[Category: Vollmar, M]]	+
-	[[Category: Weigelt, J]]	+
-	[[Category: ~~Protein kinase]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 05:51, 8 June 2022

OCA — Wed, 08 Jun 2022 05:51:56 GMT

←Older revision		Revision as of 05:51, 8 June 2022
Line 1:		Line 1:

	==Crystal structure of the ACVR1 kinase domain in complex with LDN-193189==		==Crystal structure of the ACVR1 kinase domain in complex with LDN-193189==
-	<StructureSection load='3q4u' size='340' side='right' caption='[[3q4u]], [[Resolution\|resolution]] 1.82Å' scene=''>	+	<StructureSection load='3q4u' size='340' side='right'caption='[[3q4u]], [[Resolution\|resolution]] 1.82Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3q4u]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q4U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3Q4U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3q4u]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q4U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LDN:4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE'>LDN</scene></td></tr>	+	</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=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LDN:4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE'>LDN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3mtf\|3mtf]], [[3oom\|3oom]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3mtf\|3mtf]], [[3oom\|3oom]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACVR1, ACVRLK2 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACVR1, ACVRLK2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </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=3q4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4u OCA], [~~http~~://pdbe.org/3q4u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3q4u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3q4u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3q4u ProSAT]</span></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=3q4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4u OCA], [https://pdbe.org/3q4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q4u RCSB], [https://www.ebi.ac.uk/pdbsum/3q4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q4u ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/ACVR1_HUMAN ACVR1_HUMAN]] Fibrodysplasia ossificans progressiva. Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:[~~http~~://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>	+	[[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 ==		== Function ==
-	[[~~http~~://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).	+	[[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]
	[[Category: Alfano, I]]		[[Category: Alfano, I]]

OCA at 14:47, 4 August 2016

OCA — Thu, 04 Aug 2016 14:47:02 GMT

←Older revision		Revision as of 14:47, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of the ACVR1 kinase domain in complex with LDN-193189==		==Crystal structure of the ACVR1 kinase domain in complex with LDN-193189==
	<StructureSection load='3q4u' size='340' side='right' caption='[[3q4u]], [[Resolution\|resolution]] 1.82Å' scene=''>		<StructureSection load='3q4u' size='340' side='right' caption='[[3q4u]], [[Resolution\|resolution]] 1.82Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACVR1, ACVRLK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACVR1, ACVRLK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </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=3q4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q4u RCSB], [http://www.ebi.ac.uk/pdbsum/3q4u PDBsum]</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=3q4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4u OCA], [http://pdbe.org/3q4u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3q4u RCSB], [http://www.ebi.ac.uk/pdbsum/3q4u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3q4u ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3q4u" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:23, 3 January 2015

OCA — Sat, 03 Jan 2015 21:23:57 GMT

←Older revision		Revision as of 21:23, 3 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3q4u]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q4U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q4U FirstGlance]. <br>		<table><tr><td colspan='2'>[[3q4u]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q4U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q4U FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LDN:4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE'>LDN</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LDN:4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE'>LDN</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3mtf\|3mtf]], [[3oom\|3oom]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3mtf\|3mtf]], [[3oom\|3oom]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACVR1, ACVRLK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACVR1, ACVRLK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3q4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q4u RCSB], [http://www.ebi.ac.uk/pdbsum/3q4u PDBsum]</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=3q4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q4u RCSB], [http://www.ebi.ac.uk/pdbsum/3q4u PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/ACVR1_HUMAN ACVR1_HUMAN]] Fibrodysplasia ossificans progressiva. Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:[http://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>		[[http://www.uniprot.org/uniprot/ACVR1_HUMAN ACVR1_HUMAN]] Fibrodysplasia ossificans progressiva. Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:[http://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>
Line 27:		Line 27:
	[[Category: Human]]		[[Category: Human]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]
-	[[Category: Alfano, I.]]	+	[[Category: Alfano, I]]
-	[[Category: Allerston, C K.]]	+	[[Category: Allerston, C K]]
-	[[Category: Arrowsmith, C H.]]	+	[[Category: Arrowsmith, C H]]
-	[[Category: Bountra, C.]]	+	[[Category: Bountra, C]]
-	[[Category: Bullock, A.]]	+	[[Category: Bullock, A]]
-	[[Category: Chaikuad, A.]]	+	[[Category: Chaikuad, A]]
-	[[Category: Cooper, C D.O.]]	+	[[Category: Cooper, C D.O]]
-	[[Category: Daga, N.]]	+	[[Category: Daga, N]]
-	[[Category: Delft, F von.]]	+	[[Category: Delft, F von]]
-	[[Category: Edwards, A M.]]	+	[[Category: Edwards, A M]]
-	[[Category: Fedorov, O.]]	+	[[Category: Fedorov, O]]
-	[[Category: Gileadi, O.]]	+	[[Category: Gileadi, O]]
-	[[Category: Krojer, T.]]	+	[[Category: Krojer, T]]
-	[[Category: Mahajan, P.]]	+	[[Category: Mahajan, P]]
-	[[Category: Petrie, K.]]	+	[[Category: Petrie, K]]
-	[[Category: ~~SGC,~~ Structural ~~Genomics Consortium.~~]]	+	[[Category: Structural genomic]]
-	[[Category: Sanvitale, C.]]	+	[[Category: Sanvitale, C]]
-	[[Category: Vollmar, M.]]	+	[[Category: Vollmar, M]]
-	[[Category: Weigelt, J.]]	+	[[Category: Weigelt, J]]
	[[Category: Protein kinase]]		[[Category: Protein kinase]]
	[[Category: Sgc]]		[[Category: Sgc]]
-	[[Category: Structural genomics consortium]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 05:44, 18 June 2014

OCA — Wed, 18 Jun 2014 05:44:40 GMT

←Older revision		Revision as of 05:44, 18 June 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3q4u\| PDB=3q4u \| SCENE= }}~~	+	==Crystal structure of the ACVR1 kinase domain in complex with LDN-193189==
-	===Crystal structure of the ACVR1 kinase domain in complex with LDN-193189===	+	<StructureSection load='3q4u' size='340' side='right' caption='[[3q4u]], [[Resolution\|resolution]] 1.82Å' scene=''>
-		+	== Structural highlights ==
-	==Disease==	+	<table><tr><td colspan='2'>[[3q4u]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q4U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q4U FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LDN:4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE'>LDN</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3mtf\|3mtf]], [[3oom\|3oom]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACVR1, ACVRLK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3q4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q4u RCSB], [http://www.ebi.ac.uk/pdbsum/3q4u PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/ACVR1_HUMAN ACVR1_HUMAN]] Fibrodysplasia ossificans progressiva. Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:[http://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>		[[http://www.uniprot.org/uniprot/ACVR1_HUMAN ACVR1_HUMAN]] Fibrodysplasia ossificans progressiva. Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:[http://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 ==
-	==Function==	+
	[[http://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).		[[http://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 ==
		+	Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP). Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-beta signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with K02288 and LDN-193189 revealed additional contacts in the K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development.

-	~~==About this Structure==~~	+	A new class of small molecule inhibitor of BMP signaling.,Sanvitale CE, Kerr G, Chaikuad A, Ramel MC, Mohedas AH, Reichert S, Wang Y, Triffitt JT, Cuny GD, Yu PB, Hill CS, Bullock AN PLoS One. 2013 Apr 30;8(4):e62721. doi: 10.1371/journal.pone.0062721. Print 2013. PMID:23646137<ref>PMID:23646137</ref>
-	~~[[3q4u]] is a~~ 4 ~~chain structure with sequence 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=3Q4U OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	<references ~~group="xtra"~~/><~~references~~/>	+	</div>
-	[[Category: ~~Homo sapiens~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]
	[[Category: Alfano, I.]]		[[Category: Alfano, I.]]

OCA at 08:19, 8 May 2013

OCA — Wed, 08 May 2013 08:19:45 GMT

←Older revision		Revision as of 08:19, 8 May 2013
Line 1:		Line 1:
-	[[Image:3q4u.jpg\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3q4u", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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-	-->
	{{STRUCTURE_3q4u\| PDB=3q4u \| SCENE= }}		{{STRUCTURE_3q4u\| PDB=3q4u \| SCENE= }}
-
	===Crystal structure of the ACVR1 kinase domain in complex with LDN-193189===		===Crystal structure of the ACVR1 kinase domain in complex with LDN-193189===

		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/ACVR1_HUMAN ACVR1_HUMAN]] Fibrodysplasia ossificans progressiva. Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:[http://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==
		+	[[http://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).

	==About this Structure==		==About this Structure==
	[[3q4u]] is a 4 chain structure with sequence 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=3Q4U OCA].		[[3q4u]] is a 4 chain structure with sequence 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=3Q4U OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]
Line 35:		Line 34:
	[[Category: Vollmar, M.]]		[[Category: Vollmar, M.]]
	[[Category: Weigelt, J.]]		[[Category: Weigelt, J.]]
		+	[[Category: Protein kinase]]
		+	[[Category: Sgc]]
		+	[[Category: Structural genomics consortium]]
		+	[[Category: Transferase]]

OCA at 06:14, 9 February 2011

OCA — Wed, 09 Feb 2011 06:14:18 GMT

←Older revision		Revision as of 06:14, 9 February 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3q4u.jpg\|left\|200px]]

-	The ~~entry 3q4u~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3q4u", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3q4u\| PDB=3q4u \| SCENE= }}

-	Authors: Chaikuad, A., Sanvitale, C., Cooper, C.D.O., Mahajan, P., Daga, N., Petrie, K., Alfano, I., Gileadi, O., Fedorov, O., Allerston, C., Krojer, T., Vollmar, M., von Delft, F., Weigelt, J., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Bullock, A., Structural Genomics Consortium (SGC)	+	===Crystal structure of the ACVR1 kinase domain in complex with LDN-193189===

-	~~Description: Crystal~~ structure ~~of the ACVR1 kinase domain in complex~~ with ~~LDN~~-~~193189~~	+
		+	==About this Structure==
		+	[[3q4u]] is a 4 chain structure with sequence 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=3Q4U OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Receptor protein serine/threonine kinase]]
		+	[[Category: Alfano, I.]]
		+	[[Category: Allerston, C K.]]
		+	[[Category: Arrowsmith, C H.]]
		+	[[Category: Bountra, C.]]
		+	[[Category: Bullock, A.]]
		+	[[Category: Chaikuad, A.]]
		+	[[Category: Cooper, C D.O.]]
		+	[[Category: Daga, N.]]
		+	[[Category: Delft, F von.]]
		+	[[Category: Edwards, A M.]]
		+	[[Category: Fedorov, O.]]
		+	[[Category: Gileadi, O.]]
		+	[[Category: Krojer, T.]]
		+	[[Category: Mahajan, P.]]
		+	[[Category: Petrie, K.]]
		+	[[Category: SGC, Structural Genomics Consortium.]]
		+	[[Category: Sanvitale, C.]]
		+	[[Category: Vollmar, M.]]
		+	[[Category: Weigelt, J.]]

OCA: Protected "3q4u" [edit=sysop:move=sysop]

OCA — Wed, 05 Jan 2011 15:55:50 GMT

Protected "3q4u" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:55, 5 January 2011

OCA: New page: '''Unreleased structure''' The entry 3q4u is ON HOLD Authors: Chaikuad, A., Sanvitale, C., Cooper, C.D.O., Mahajan, P., Daga, N., Petrie, K., Alfano, I., Gileadi, O., Fedorov, O., Aller...

OCA — Wed, 05 Jan 2011 15:55:49 GMT

New page: '''Unreleased structure''' The entry 3q4u is ON HOLD Authors: Chaikuad, A., Sanvitale, C., Cooper, C.D.O., Mahajan, P., Daga, N., Petrie, K., Alfano, I., Gileadi, O., Fedorov, O., Aller...

New page

'''Unreleased structure'''

The entry 3q4u is ON HOLD

Authors: Chaikuad, A., Sanvitale, C., Cooper, C.D.O., Mahajan, P., Daga, N., Petrie, K., Alfano, I., Gileadi, O., Fedorov, O., Allerston, C., Krojer, T., Vollmar, M., von Delft, F., Weigelt, J., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Bullock, A., Structural Genomics Consortium (SGC)

Description: Crystal structure of the ACVR1 kinase domain in complex with LDN-193189