Identification of Non-Phosphate-Containing Small Molecular Weight Inhibitors of the Tyrosine Kinase p56 Lck SH2 Domain via in Silico Screening against the pY + 3 Binding Site

2004 ◽  
Vol 47 (14) ◽  
pp. 3502-3511 ◽  
Author(s):  
Niu Huang ◽  
Ashish Nagarsekar ◽  
Guanjun Xia ◽  
Jun Hayashi ◽  
Alexander D. MacKerell
Keyword(s):  
Molecular Weight ◽  
Tyrosine Kinase ◽  
Binding Site ◽  
In Silico ◽  
Sh2 Domain ◽  
Small Molecular Weight ◽  
In Silico Screening

scholarly journals The Selectivity of Receptor Tyrosine Kinase Signaling Is Controlled by a Secondary SH2 Domain Binding Site

Cell ◽  
2009 ◽  
Vol 138 (3) ◽  
pp. 514-524 ◽  
Author(s):  
Jae Hyun Bae ◽  
Erin Denise Lew ◽  
Satoru Yuzawa ◽  
Francisco Tomé ◽  
Irit Lax ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Binding Site ◽  
Receptor Tyrosine Kinase ◽  
Sh2 Domain ◽  
Kinase Signaling ◽  
Tyrosine Kinase Signaling

Design and Synthesis of Non-peptidic Inhibitors for the Syk C-Terminal SH2 Domain Based on Structure-Based In-Silico Screening

2001 ◽  
Vol 44 (26) ◽  
pp. 4737-4740 ◽  
Author(s):  
Tatsuya Niimi ◽  
Masaya Orita ◽  
Miwa Okazawa-Igarashi ◽  
Hitoshi Sakashita ◽  
Kazumi Kikuchi ◽  
...  
Keyword(s):  
In Silico ◽  
Sh2 Domain ◽  
In Silico Screening ◽  
Design And Synthesis ◽  
Peptidic Inhibitors

scholarly journals Integrin cytoplasmic domain and pITAM compete for spleen tyrosine kinase binding

2019 ◽  
Author(s):  
Lina Antenucci ◽  
Maarit Hellman ◽  
Vesa P. Hytönen ◽  
Perttu Permi ◽  
Jari Ylänne
Keyword(s):  
Cell Adhesion ◽  
Tyrosine Kinase ◽  
Binding Site ◽  
Conformational Changes ◽  
Cytoplasmic Domain ◽  
Sh2 Domain ◽  
Regulatory Domain ◽  
Spleen Tyrosine Kinase ◽  
Adhesion Receptors ◽  
Sh2 Domains

ABSTRACTIn hematopoietic tissues cell-cell communication involves immunoreceptors and specialized cell adhesion receptors that both mediate intracellular signals. Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase involved in the downstream signaling of both immunoreceptors tyrosine activation motif (ITAM) receptors and integrin family cell adhesion receptors. Both phosphorylated ITAM (pITAM) and integrins bind to the regulatory domain of Syk composed of two Src homology 2 (SH2) domains. The interaction with pITAM is mediated by binding of a specific phosphotyrosine to each of the SH2 domains, leading to conformational changes and Syk kinase activation. Integrins bind to the interdomain A segment between the two SH2 domains and to the N-terminal SH2 domain, but the detailed binding site is not known. In order to map the binding site, we performed NMR titration experiments. We found that integrin cytoplasmic domain peptide induced chemical shift changes near the IA segment and at the phosphotyrosine binding site of the N-terminal SH2 domain of Syk. These changes were distinct, but partially overlapping with those induced by pITAM peptide. We were also able to show that pITAM peptide inhibited integrin binding to Syk regulatory domain. These results suggest that ITAM receptors and integrins cannot bind simultaneously to Syk, but provide two distinct routes for Syk activation.

In-silico screening of 2,3-diphenylquinozaline derivatives as C-met kinase inhibitors

2017 ◽  
Vol 4 (3) ◽  
pp. 41-45
Author(s):  
Nehla Yahcoob ◽  
Baskar Lakshmanan ◽  
Jyothi Achuthanandhan ◽  
Vijayakumar Balakrishnan
Keyword(s):  
Binding Energy ◽  
Tyrosine Kinase ◽  
In Silico ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Binding Interaction ◽  
In Silico Screening ◽  
Sar Study

Quinoxaline, an important class of heterocylic compounds drawn greater attention due to their wide spectrum of biological activities. They are considered as an important chemical scaffold for anticancer drug design  due to their potential inhibitory activity against  C-met tyrosine kinase. C-met kinase inhibitors  are a class of small molecules that having therapeutic potential in  the treatment of various types of cancers. The present study aims to focus on the chemistry of quinoxaline derivatives, their potential activities against C-met tyrosine kinase, and in-silico screening of designed compounds. A series of twelve compounds were designed and docked against C-met tyrosine kinase for their binding energy. All compounds were found to be interacting  well with the protein. Compound NQ1 was found to have good binding energy showing an estimated Ki value of  1.1μm.  SAR  study indicated the presence of an electron withdrawing substitution on  benzilidine  phenyl ring of quinoxaline greatly improves its binding interaction with the protein.

scholarly journals A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase.

1995 ◽  
Vol 15 (9) ◽  
pp. 4810-4818 ◽  
Author(s):  
K M Lai ◽  
J P Olivier ◽  
G D Gish ◽  
M Henkemeyer ◽  
J McGlade ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Binding Site ◽  
Receptor Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Adaptor Protein ◽  
Sh2 Domain ◽  
Expression Library ◽  
Close Relationship ◽  
Ptb Domain

Antibodies to the human Shc adaptor protein were used to isolate a cDNA encoding a Drosophila Shc protein (dShc) by screening an expression library. The dshc gene, which maps to position 67B-C on the third chromosome, encodes a 45-kDa protein that is widely expressed throughout the Drosophila life cycle. In flies, the dShc protein physically associates with the activated Drosophila epidermal growth factor receptor homolog (DER) and is inducibly phosphorylated on tyrosine by DER. The 45-kDa dShc protein is closely related both in overall organization and in amino acid sequence (46% identity) to the 52-kDa mammalian Shc isoform. In addition to a C-terminal Src homology 2 (SH2) domain, dShc contains an N-terminal phosphotyrosine-binding (PTB) domain, which associates in vitro with the autophosphorylated DER receptor tyrosine kinase and with phosphopeptides containing an Asn-Pro-X-pTyr motif, where pTyr stands for phosphotyrosine. A potential binding site for the dShc PTB domain is located at Tyr-1228 of DER. These results indicate that the shc gene has been conserved in evolution, as have the binding properties of the Shc PTB and SH2 domains. Despite the close relationship between the Drosophila and mammalian Shc proteins, dShc lacks the high-affinity Grb2-binding site found in mammalian Shc, suggesting that Shc proteins may have functions in addition to regulation of the Ras pathway.

The Selectivity of Receptor Tyrosine Kinase Signaling Is Controlled by a Secondary SH2 Domain Binding Site

2009 ◽  
Vol 138 (33) ◽  
pp. 514-524
Author(s):  
Jae Hyun Bae ◽  
Erin Denise Lew ◽  
Satoru Yuzawa ◽  
Francisco Tomé ◽  
Irit Lax ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Binding Site ◽  
Receptor Tyrosine Kinase ◽  
Sh2 Domain ◽  
Kinase Signaling ◽  
Tyrosine Kinase Signaling

The Selectivity of Receptor Tyrosine Kinase Signaling Is Controlled by a Secondary SH2 Domain Binding Site

2009 ◽  
Vol 138 (3) ◽  
pp. 514-524
Author(s):  
Jae Hyun Bae ◽  
Erin Denise Lew ◽  
Satoru Yuzawa ◽  
Francisco Tomé ◽  
Irit Lax ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Binding Site ◽  
Receptor Tyrosine Kinase ◽  
Sh2 Domain ◽  
Kinase Signaling ◽  
Tyrosine Kinase Signaling
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