Proteopedia

5dc0: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5dc0]] 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=5DC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DC0 FirstGlance]. <br>
<table><tr><td colspan='2'>[[5dc0]] 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=5DC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DC0 FirstGlance]. <br>
</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=5dc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dc0 OCA], [https://pdbe.org/5dc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dc0 RCSB], [https://www.ebi.ac.uk/pdbsum/5dc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dc0 ProSAT]</span></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]] 2.23&#8491;</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=5dc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dc0 OCA], [https://pdbe.org/5dc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dc0 RCSB], [https://www.ebi.ac.uk/pdbsum/5dc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dc0 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>  Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>  
[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>  Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>  
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== Publication Abstract from PubMed ==
Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia (CML). We have shown that a tandem fusion of two designed binding proteins, termed monobodies, respectively directed to the interaction interface between the SH2 and kinase domains and to the phosphotyrosine-binding site of the SH2 domain inhibits the of Bcr-Abl kinase activity. Because the latter monobody inhibits processive phosphorylation by Bcr-Abl and the SH2-kinase interface is occluded in the active kinase, it remained undetermined whether targeting the SH2-kinase interface alone was sufficient for Bcr-Abl inhibition. To address this question, we generated new, higher-affinity monobodies, with single nanomolar KD values, targeting the kinase-binding surface of SH2. Structural and mutagenesis studies revealed the molecular underpinnings of the monobody-SH2 interactions. Importantly, the new monobodies inhibited Bcr-Abl kinase activity in vitro and in cells, and they potently induced cell death in CML cell lines. This work provides strong evidence for the SH2-kinase interface as a pharmacologically tractable site for allosteric inhibition of Bcr-Abl.
Allosteric Inhibition of Bcr-Abl Kinase by High-Affinity Monobody Inhibitors Directed to the SH2-Kinase Interface.,Wojcik J, Lamontanara AJ, Grabe G, Koide A, Akin L, Gerig B, Hantschel O, Koide S J Biol Chem. 2016 Feb 24. pii: jbc.M115.707901. PMID:26912659<ref>PMID:26912659</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5dc0" style="background-color:#fffaf0;"></div>


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

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OCA
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