View source for 4lgh


==Crystal structure of 1NM-PP1 bound to analog-sensitive Src kinase==
<StructureSection load='4lgh' size='340' side='right'caption='[[4lgh]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4lgh]] 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=4LGH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LGH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JN:1-TERT-BUTYL-3-(NAPHTHALEN-1-YLMETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>0JN</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=4lgh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lgh OCA], [https://pdbe.org/4lgh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lgh RCSB], [https://www.ebi.ac.uk/pdbsum/4lgh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lgh ProSAT]</span></td></tr>
</table>
== Function ==
[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 ==
Engineered analog-sensitive (AS) protein kinases have emerged as powerful tools for dissecting phospho-signaling pathways, for elucidating the cellular function of individual kinases, and for deciphering unanticipated effects of clinical therapeutics. A crucial and necessary feature of this technology is a bioorthogonal small molecule that is innocuous toward native cellular systems but potently inhibits the engineered kinase. In order to generalize this method, we sought a molecule capable of targeting divergent AS-kinases. Here we employ X-ray crystallography and medicinal chemistry to unravel the mechanism of current inhibitors and use these insights to design the most potent, selective, and general AS-kinase inhibitors reported to date. We use large-scale kinase inhibitor profiling to characterize the selectivity of these molecules as well as examine the consequences of potential off-target effects in chemical genetic experiments. The molecules reported here will serve as powerful tools in efforts to extend AS-kinase technology to the entire kinome and the principles discovered may help in the design of other engineered enzyme/ligand pairs.

Structure-Guided Inhibitor Design Expands the Scope of Analog-Sensitive Kinase Technology.,Zhang C, Lopez MS, Dar AC, Ladow E, Finkbeiner S, Yun CH, Eck MJ, Shokat KM ACS Chem Biol. 2013 Jul 23. PMID:23841803<ref>PMID:23841803</ref>

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

==See Also==
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Dar AC]]
[[Category: Lopez MS]]
[[Category: Shokat KM]]