Title

Authors

Affiliation

¹Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Jl Veteran, Malang, East Java 65145, Indonesia; ²Department of Endocrinology, Saeful Anwar Hospital, Jl. Jaksa Agung Suprapto No. 2 Malang, East Java, Indonesia

Email

fatchiya@gmail.com; *Corresponding author

Article Type

Hypothesis

Date

Received September 27, 2013; Accepted September 30, 2013; Published October 16, 2013

The purpose of this study is to examine the effect of mutation on tyrosine kinase hINSR gene of DM Type 2 patients reduce the IRS-1 activation by in silico analysis. Blood DNA of DM Type 2 patients from Saeful Anwar Hospital Malang were amplified and sequenced by specific primers of tyrosine kinase domain of hINSR gene. These gene sequences were converted to protein sequence by BLAST and the IRS-1 protein sequence is retrieved from NCBI database. Both of the protein sequence was aligned by using Bio-edit version 5.0.6. The model of three dimension protein was predicted by SWISS MODEL webserver, and visualized the structure alteration by using Pymol 0.99rc6 and Hex 5.0, and then superimpose of the hINSR and IRS-1 interaction were examined by docking using Hex 5.0. The results showed that one substitution and one deletion of 8-3F patient exon-22 hINSR gene tyrosine kinase domain cause loss of four helixes and three coils structures on tyrosine kinase hINSR protein. Six-deletions and six-substitutions on same gene domain of DMK9 patient changed the two helixes became coil structure. The binding energy of hINSR tyrosine kinase with IRS-1 of normal is E= -494.67 kJ/mol, DMK9 patient is E= -458.4 kJ/mol, and 8-3F patient is E=-544.20 kJ/mol. The DMK9 patient prognosis has better physiological condition than 8-3F patient. Interaction between 8-3F of hINSR tyrosine kinase domain mutation and PTB domain IRS-1 is more spontaneous than DMK9, but both of them were reduced on IRS-1 activation respectively.

Keywords

Diabetes Mellitus Type-2, hINSR, In Silico, IRS-1

Citation

Fatchiyah et al.  Bioinformation 9(17): 853-857 (2013)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.