apoptin 3d modeling abstract (kelas bioinformatika).pdf
TRANSCRIPT
HOMOLOGY MODELING OF MOLECULAR INTERACTION
BETWEEN APOPTIN WITH C-TERMINAL POLYHISTIDINE AND
BCR-ABL ONCOPROTEIN: A MEAN TO ANALYZE APOPTIN-
MODIFIED ACTIVE SITE
O. Sahat1, G. Ramadhan1, P. Rachman1, A. Wiseso1, E. Dian Kamila1, V. Geraldine1, M.
Chandra P1, T. Hidayat A1, M. Sahlan3 A. Yanuar2, and M. Gozan3
1. Society of Biological Engineering (SBE) Universitas Indonesia Student Chapter, Universitas
Indonesia, Kampus Depok 16424, Indonesia
2. Department of Chemical Engineering, Faculty of Engineering, Universitas Indonesia, Kampus Depok 16424,
Indonesia
3. Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok 16424, Indonesia.
E-mail: [email protected]
Abstract
Apoptin, derived from chicken anemia virus (CAV), is a small protein, which possess the ability to induce
apoptosis in cells through subcellular localization. It belongs to the Gyrovirus genus and Circoviridae family
and contains a single, minus-strand circular DNA; often linked with various cellular proteins that has roles in
cell proliferation and cell death. Despite its great attention of its ability to trigger apoptosis, the mechanism of
action of apoptin remains equivocal. However, it is still lucid that apoptin can trigger tumor-selective apoptosis.
To be expressed as a recombinant protein, a 12-his tag was added to the C-terminal, whilst a Shine Dalgarno
(SD) promoter sequence and an ATG start codon were added to the N-terminal region preceding the apoptin
structural gene. By fusing apoptin with 12-histidine to the C-terminal end, the solubility of apoptin in buffer
could be improved. In this study, we performed homology modeling of both apoptin and apoptin fused with 12-
histidine using L-asparaginase from Archaceae (1WNF_A PH0066) as the template. We perform sequence
alignment of our sequence target and template, subsequently validate the homology modeling result by several
parameters, including Z-value and Ramachandran plot, and compare the results attained. The comparison is
carried out by docking both apoptins with Bcr-Abl oncoprotein to ponder whether the active site of apoptin
fused with 12-his tag undergoes tangible modifications which may alter its interactions with Bcr-Abl
oncoprotein. This model is anticipated as a guide in developing a new class of apoptin-modified molecules with
greater potential and selectivity.
Keywords: Apoptin, , homology modeling, 1WNF_A, 12-histidine, Bcr-Abl oncoprotein