Structural and functional analysis of KIT gene encoding receptor tyrosine kinase and its interaction with sunitinib and HDAC inhibitors: an in silico approach.

@article{Vanajothi2012StructuralAF,
  title={Structural and functional analysis of KIT gene encoding receptor tyrosine kinase and its interaction with sunitinib and HDAC inhibitors: an in silico approach.},
  author={Ramar Vanajothi and Sundararaj Rajamanikandan and Arumugam Sudha and Pappu Srinivasan},
  journal={Pakistan journal of biological sciences : PJBS},
  year={2012},
  volume={15 3},
  pages={
          121-31
        }
}
KIT is a growth factor receptor, important for normal germ cell migration and development. The malfunction of KIT gene results in constitutive activation of the tyrosine kinase activity of c-KIT which is believed to be the major oncogenic event in stomach, small intestine mastocytosis, acute leukemias, melanomas and colon tumors. The genetics of these diseases could be better understood by knowing the functional relevance of their SNP variation. In this study, a computational analysis to detect… 

Prediction of the Damage-Associated Non-Synonymous Single Nucleotide Polymorphisms in the Human MC1R Gene

The computational analysis proved capable of identifying the potentially damaging nsSNPs in MC1R, which are candidates for further laboratory studies of the functional and pharmacological significance of the alterations in the receptor and the phenotypic outcomes.

Prediction of deleterious non-synonymous SNPs of human TLR2 gene associated with bacterial meningitis and hearing impairment by computational approach

  • P. Manikandan
  • Biology, Medicine
    International journal of health sciences
  • 2022
The coding and non-coding SNPs of the human TLR2 gene was retrieved from the NCBI database and were subjected to various computational prediction tools to predict the high-risk deleterious SNPs and the effect of single amino acid substitutions and structural and functional impact of these mutations was predicted with project HOPE, SNP-GO tools.

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It is demonstrated that the signal transduction pathways mediated by c-Kit/D816V are markedly different from those activated by wild-type c- Kit and that altered substrate specificity ofc-Kit circumvents a need for Src family kinases in signaling of growth and survival, thereby contributing to the transforming potential of c-kit/D 816V.

Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in gastrointestinal stromal tumors.

Results provide preclinical evidence for a disease-specific effect of HDACI in KIT-positive GIST, which could translate into therapeutic activity.

Structure of a c-Kit Product Complex Reveals the Basis for Kinase Transactivation*

The results provide key insights into the molecular basis for c-Kit kinase transactivation to assist in the design of new competitive inhibitors targeting activated mutant forms of c- Kit that are resistant to current chemotherapy regimes.

Structural Basis for the Autoinhibition and STI-571 Inhibition of c-Kit Tyrosine Kinase*

The 1.9-Å resolution crystal structure of native c-Kit kinase in an autoinhibited conformation is reported and will facilitate the structure-guided design of specific inhibitors that target the activated andAutoinhibited conformations of c- Kit kinase.

Mutations in Exon 11 of the c-kit Gene in a Myogenic Tumor and a Neurogenic Tumor as Well as in Gastrointestinal Stromal Tumors

It is concluded that the gain-of-function mutation in exon 11 of the c-kit gene is an important prognostic factor for gastrointestinal mesenchymal tumors, including myogenic and neurogenic tumors as well as GISTs.

Signalling by the W/Kit receptor tyrosine kinase is negatively regulated in vivo by the protein tyrosine phosphatase Shp1

DNA analysis in mammals shows that homozygosity for mutations in both W and me ameliorates aspects of both the me and W phenotypes, demonstrating that the Kit receptor plays a role in the pathology of the me phenotype and conversely that Shp1 negatively regulates Kit signalling in vivo.