2c0t: Difference between revisions

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[[Image:2c0t.gif|left|200px]]


{{Structure
==Src family kinase Hck with bound inhibitor A-641359==
|PDB= 2c0t |SIZE=350|CAPTION= <scene name='initialview01'>2c0t</scene>, resolution 2.15&Aring;
<StructureSection load='2c0t' size='340' side='right'caption='[[2c0t]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:Ca+Binding+Site+For+Chain+B'>AC1</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=L3G:N-(4-{4-AMINO-1-[1-(TETRAHYDRO-2H-PYRAN-4-YL)PIPERIDIN-4-YL]-1H-PYRAZOLO[3,4-D]PYRIMIDIN-3-YL}-2-METHOXYPHENYL)-1-METHYL-1H-INDOLE-2-CARBOXAMIDE'>L3G</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>
<table><tr><td colspan='2'>[[2c0t]] 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=2C0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C0T FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
|GENE=
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=L3G:N-(4-{4-AMINO-1-[1-(TETRAHYDRO-2H-PYRAN-4-YL)PIPERIDIN-4-YL]-1H-PYRAZOLO[3,4-D]PYRIMIDIN-3-YL}-2-METHOXYPHENYL)-1-METHYL-1H-INDOLE-2-CARBOXAMIDE'>L3G</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c0t OCA], [https://pdbe.org/2c0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c0t RCSB], [https://www.ebi.ac.uk/pdbsum/2c0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c0t ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c0t OCA], [http://www.ebi.ac.uk/pdbsum/2c0t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c0t RCSB]</span>
== Disease ==
}}
[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>  Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>
== Function ==
[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c0/2c0t_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2c0t ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days.


'''SRC FAMILY KINASE HCK WITH BOUND INHIBITOR A-641359'''
Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection.,Burchat A, Borhani DW, Calderwood DJ, Hirst GC, Li B, Stachlewitz RF Bioorg Med Chem Lett. 2006 Jan 1;16(1):118-22. Epub 2005 Oct 10. PMID:16216497<ref>PMID:16216497</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2c0t" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days.
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
 
== References ==
==About this Structure==
<references/>
2C0T is a [[Single protein]] structure of 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=2C0T OCA].
__TOC__
 
</StructureSection>
==Reference==
Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection., Burchat A, Borhani DW, Calderwood DJ, Hirst GC, Li B, Stachlewitz RF, Bioorg Med Chem Lett. 2006 Jan 1;16(1):118-22. Epub 2005 Oct 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16216497 16216497]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Transferase]]
[[Category: Borhani DW]]
[[Category: Borhani, D W.]]
[[Category: Burchat A]]
[[Category: Burchat, A.]]
[[Category: Calderwood DJ]]
[[Category: Calderwood, D J.]]
[[Category: Hirst GC]]
[[Category: Hirst, G C.]]
[[Category: Li B]]
[[Category: Li, B.]]
[[Category: Loew A]]
[[Category: Loew, A.]]
[[Category: alternative initiation]]
[[Category: atp-binding]]
[[Category: kinase]]
[[Category: lipoprotein]]
[[Category: myristate]]
[[Category: nucleotide-binding]]
[[Category: palmitate]]
[[Category: phosphorylation]]
[[Category: sh2 domain]]
[[Category: sh3 domain]]
[[Category: transferase]]
[[Category: tyrosine-protein kinase]]
 
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