4rss - Revision history

OCA at 09:00, 20 March 2024

2024-03-20T09:00:06Z

← Older revision		Revision as of 09:00, 20 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rss]] is a 1 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=4RSS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RSS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rss]] is a 1 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=4RSS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RSS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4MG:1-[(3-METHYL-1-{2-[(1,2,3-TRIMETHYL-1H-INDOL-5-YL)AMINO]PYRIMIDIN-4-YL}-1H-PYRAZOL-4-YL)METHYL]AZETIDIN-3-OL'>4MG</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]] 1.83Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4MG:1-[(3-METHYL-1-{2-[(1,2,3-TRIMETHYL-1H-INDOL-5-YL)AMINO]PYRIMIDIN-4-YL}-1H-PYRAZOL-4-YL)METHYL]AZETIDIN-3-OL'>4MG</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=4rss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rss OCA], [https://pdbe.org/4rss PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rss RCSB], [https://www.ebi.ac.uk/pdbsum/4rss PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rss 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=4rss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rss OCA], [https://pdbe.org/4rss PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rss RCSB], [https://www.ebi.ac.uk/pdbsum/4rss PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rss ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/KSYK_HUMAN KSYK_HUMAN] Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. Beside its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen.<ref>PMID:8657103</ref> <ref>PMID:9535867</ref> <ref>PMID:12456653</ref> <ref>PMID:12387735</ref> <ref>PMID:15388330</ref> <ref>PMID:19909739</ref>		[https://www.uniprot.org/uniprot/KSYK_HUMAN KSYK_HUMAN] Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. Beside its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen.<ref>PMID:8657103</ref> <ref>PMID:9535867</ref> <ref>PMID:12456653</ref> <ref>PMID:12387735</ref> <ref>PMID:15388330</ref> <ref>PMID:19909739</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectivity. Lead optimization efforts provided compounds with potent Syk inhibition in both enzymatic and TNF-alpha release assay.

	Highly potent and selective pyrazolylpyrimidines as Syk kinase inhibitors.,Choi JS, Hwang HJ, Kim SW, Lee BI, Lee J, Song HJ, Koh JS, Kim JH, Lee PH Bioorg Med Chem Lett. 2015 Oct 15;25(20):4441-6. doi: 10.1016/j.bmcl.2015.09.011., Epub 2015 Sep 8. PMID:26384287<ref>PMID:26384287</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4rss" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==

OCA at 08:27, 8 March 2023

2023-03-08T08:27:18Z

← Older revision		Revision as of 08:27, 8 March 2023
Line 3:		Line 3:
	<StructureSection load='4rss' size='340' side='right'caption='[[4rss]], [[Resolution\|resolution]] 1.83Å' scene=''>		<StructureSection load='4rss' size='340' side='right'caption='[[4rss]], [[Resolution\|resolution]] 1.83Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rss]] is a 1 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=4RSS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RSS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rss]] is a 1 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=4RSS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RSS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4MG:1-[(3-METHYL-1-{2-[(1,2,3-TRIMETHYL-1H-INDOL-5-YL)AMINO]PYRIMIDIN-4-YL}-1H-PYRAZOL-4-YL)METHYL]AZETIDIN-3-OL'>4MG</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4MG:1-[(3-METHYL-1-{2-[(1,2,3-TRIMETHYL-1H-INDOL-5-YL)AMINO]PYRIMIDIN-4-YL}-1H-PYRAZOL-4-YL)METHYL]AZETIDIN-3-OL'>4MG</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SYK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4rss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rss OCA], [https://pdbe.org/4rss PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rss RCSB], [https://www.ebi.ac.uk/pdbsum/4rss PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rss ProSAT]</span></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=4rss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rss OCA], [~~http~~://pdbe.org/4rss PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4rss RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4rss PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4rss ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/KSYK_HUMAN KSYK_HUMAN]] Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. Beside its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen.<ref>PMID:8657103</ref> <ref>PMID:9535867</ref> <ref>PMID:12456653</ref> <ref>PMID:12387735</ref> <ref>PMID:15388330</ref> <ref>PMID:19909739</ref>		[https://www.uniprot.org/uniprot/KSYK_HUMAN KSYK_HUMAN] Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. Beside its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen.<ref>PMID:8657103</ref> <ref>PMID:9535867</ref> <ref>PMID:12456653</ref> <ref>PMID:12387735</ref> <ref>PMID:15388330</ref> <ref>PMID:19909739</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific protein-tyrosine kinase]]~~		[[Category: Choi J-S]]
	[[Category: Choi, J S]]		[[Category: Lee BI]]
	[[Category: Lee~~, B I~~]]		[[Category: Lee SJ]]
	[[Category: Lee~~, S J]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 10:10, 1 May 2019

2019-05-01T10:10:09Z

← Older revision		Revision as of 10:10, 1 May 2019
Line 1:		Line 1:

	==Crystal structure of tyrosine-protein kinase SYK with an inhibitor==		==Crystal structure of tyrosine-protein kinase SYK with an inhibitor==
	<StructureSection load='4rss' size='340' side='right' caption='[[4rss]], [[Resolution\|resolution]] 1.83Å' scene=''>		<StructureSection load='4rss' size='340' side='right'caption='[[4rss]], [[Resolution\|resolution]] 1.83Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rss]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RSS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RSS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rss]] is a 1 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=4RSS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RSS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4MG:1-[(3-METHYL-1-{2-[(1,2,3-TRIMETHYL-1H-INDOL-5-YL)AMINO]PYRIMIDIN-4-YL}-1H-PYRAZOL-4-YL)METHYL]AZETIDIN-3-OL'>4MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4MG:1-[(3-METHYL-1-{2-[(1,2,3-TRIMETHYL-1H-INDOL-5-YL)AMINO]PYRIMIDIN-4-YL}-1H-PYRAZOL-4-YL)METHYL]AZETIDIN-3-OL'>4MG</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SYK ([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/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=4rss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rss OCA], [http://pdbe.org/4rss PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rss RCSB], [http://www.ebi.ac.uk/pdbsum/4rss 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=4rss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rss OCA], [http://pdbe.org/4rss PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rss RCSB], [http://www.ebi.ac.uk/pdbsum/4rss PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rss ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4rss" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4rss" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Tyrosine kinase\|Tyrosine kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Choi, J S]]		[[Category: Choi, J S]]

OCA at 05:22, 22 October 2015

2015-10-22T05:22:51Z

← Older revision		Revision as of 05:22, 22 October 2015
Line 1:		Line 1:
	'''~~Unreleased~~ structure'''		==Crystal structure of tyrosine-protein kinase SYK with an inhibitor==
			<StructureSection load='4rss' size='340' side='right' caption='[[4rss]], [[Resolution\|resolution]] 1.83Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4rss]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RSS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RSS FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4MG:1-[(3-METHYL-1-{2-[(1,2,3-TRIMETHYL-1H-INDOL-5-YL)AMINO]PYRIMIDIN-4-YL}-1H-PYRAZOL-4-YL)METHYL]AZETIDIN-3-OL'>4MG</scene></td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=4rss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rss OCA], [http://pdbe.org/4rss PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rss RCSB], [http://www.ebi.ac.uk/pdbsum/4rss PDBsum]</span></td></tr>
			</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/KSYK_HUMAN KSYK_HUMAN]] Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. Beside its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen.<ref>PMID:8657103</ref> <ref>PMID:9535867</ref> <ref>PMID:12456653</ref> <ref>PMID:12387735</ref> <ref>PMID:15388330</ref> <ref>PMID:19909739</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectivity. Lead optimization efforts provided compounds with potent Syk inhibition in both enzymatic and TNF-alpha release assay.

	~~The entry 4rss is ON HOLD until Paper Publication~~		Highly potent and selective pyrazolylpyrimidines as Syk kinase inhibitors.,Choi JS, Hwang HJ, Kim SW, Lee BI, Lee J, Song HJ, Koh JS, Kim JH, Lee PH Bioorg Med Chem Lett. 2015 Oct 15;25(20):4441-6. doi: 10.1016/j.bmcl.2015.09.011., Epub 2015 Sep 8. PMID:26384287<ref>PMID:26384287</ref>

	~~Authors: Lee~~, ~~B.I~~.~~, Lee,~~ S.~~J., Choi, J~~.-S.		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~Description~~: ~~Crystal structure of tyrosine~~-protein kinase ~~SYK with an inhibitor~~		<div class="pdbe-citations 4rss" style="background-color:#fffaf0;"></div>
	[[Category: ~~Unreleased Structures~~]]		== References ==
	[[Category: Lee, B.I]]		<references/>
	[[Category: ~~Choi~~, J~~.-S~~]]		__TOC__
	[[Category: ~~Lee, S.J~~]]		</StructureSection>
			[[Category: Non-specific protein-tyrosine kinase]]
			[[Category: Choi, J S]]
			[[Category: Lee, B I]]
			[[Category: Lee, S J]]
			[[Category: Kinase]]
			[[Category: Transferase-transferase inhibitor complex]]

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New page: '''Unreleased structure''' The entry 4rss is ON HOLD Authors: Lee, B.I., Lee, S.J., Choi, J-S. Description: Crystal structure of tyrosine-protein kinase SYK with an inhibitor

New page

'''Unreleased structure'''

The entry 4rss is ON HOLD

Authors: Lee, B.I., Lee, S.J., Choi, J-S.

Description: Crystal structure of tyrosine-protein kinase SYK with an inhibitor