6wiw

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:44, 6 March 2024) (edit) (undo)
 
Line 3: Line 3:
<StructureSection load='6wiw' size='340' side='right'caption='[[6wiw]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='6wiw' size='340' side='right'caption='[[6wiw]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[6wiw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WIW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WIW FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[6wiw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WIW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WIW FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I14:N-(3-{[4-amino-7-(2-methoxyethyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl}-4-methylphenyl)acetamide'>I14</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]] 2.3&#8491;</td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I14:N-(3-{[4-amino-7-(2-methoxyethyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl}-4-methylphenyl)acetamide'>I14</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'>[https://proteopedia.org/fgij/fg.htm?mol=6wiw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wiw OCA], [https://pdbe.org/6wiw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wiw RCSB], [https://www.ebi.ac.uk/pdbsum/6wiw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wiw ProSAT]</span></td></tr>
-
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wiw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wiw OCA], [http://pdbe.org/6wiw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wiw RCSB], [http://www.ebi.ac.uk/pdbsum/6wiw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wiw ProSAT]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK]] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref>
+
[https://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref>
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
Small molecule kinase inhibitors that stabilize distinct ATP-binding site conformations can differentially modulate the global conformation of Src-family kinases (SFKs). However, it is unclear which specific ATP-binding site contacts are responsible for modulating the global conformation of Src-family kinases (SFKs) and whether these inhibitor-mediated allosteric effects are general to other tyrosine kinases. Here, we describe the development of chemical probes that allow us to deconvolute which features in the ATP-binding site are responsible for the allosteric modulation of the global conformation of Src. We find that the ability of an inhibitor to modulate the global conformation of Src's regulatory domain-catalytic domain module relies mainly on the influence it has on the conformation of a structural element called helix C. Furthermore, by developing a set of orthogonal probes that target a drug-sensitized Src variant, we show that stabilizing Src's helix C in an active conformation is sufficient to promote a Src-mediated, phosphotransferase-independent alteration in cell morphology. Finally, we report that ATP-competitive, conformation-selective inhibitors can influence the global conformation of tyrosine kinases beyond the SFKs, suggesting that the allosteric networks we observe in Src are conserved in kinases that have a similar regulatory architecture. Taken together, our study highlights that an ATP-competitive inhibitor's interactions with helix C can have a major influence on the global conformation of some tyrosine kinases in vitro and in cells.
+
-
 
+
-
How ATP-competitive inhibitors allosterically modulate tyrosine kinases that contain a Src-like regulatory architecture.,Fang L, Vilas-Boas J, Chakraborty S, Potter ZE, Register AC, Seeliger MA, Maly DJ ACS Chem Biol. 2020 Jun 1. doi: 10.1021/acschembio.0c00429. PMID:32479050<ref>PMID:32479050</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 6wiw" style="background-color:#fffaf0;"></div>
+
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Chick]]
+
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Non-specific protein-tyrosine kinase]]
+
[[Category: Fang L]]
-
[[Category: Fang, L]]
+
[[Category: Maly D]]
-
[[Category: Maly, D]]
+
[[Category: Seeliger MA]]
-
[[Category: Seeliger, M A]]
+
[[Category: Thakur MK]]
-
[[Category: Thakur, M K]]
+
[[Category: Vilas-Boas J]]
-
[[Category: Vilas-Boas, J]]
+
-
[[Category: Complex]]
+
-
[[Category: Inhibitor]]
+
-
[[Category: Kinase]]
+
-
[[Category: Src]]
+
-
[[Category: Transferase]]
+
-
[[Category: Transferase-inhibitor complex]]
+

Current revision

c-Src Bound to ATP-Competitive Inhibitor I14

PDB ID 6wiw

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools