In silico Study of Isozyme Human DNA Topoisomerase II Conserve Region Etoposite Binding Domain...

In silico Study of Isozyme Human DNA Topoisomerase II Conserve Region Etoposite Binding Domain, 

ABSTRACT

DNA topoisomerase II (Top2) is essential enzyme that solves the topological problems of DNA. Top2A and Top2B are two kind of Top2 in human. Top2A is expressed at differentiation active cells as cancer cells whereas Top2B is expressed at non differentiation cells or quiescent cells. Their critical role makes Top2B an attractive drug target against cancer as etoposite known as Top2 inhibitor. Active site for etoposite binding domain to Top2B has been done but in Top2A has not been done yet. Conserve region study by multiple sequence alignment between Top2A and Top2B as Top2B to be a template was aimed to search an active site for etoposite binding domain in Top2A. A conserve amino acid area with highest similarity was used to predict essential amino acid activity in the enzyme. Homology study shows that Top2A and Top2B have the same similarity of amino acids of 80% with structure similarity of 71.81%. Active amino acids on Top2B for etoposite binding domain such as Gly478, Asp479, Arg503, Met782 dan Gln778 were found to be highly conserve with amino acid Gly462, Asp463, Arg487, Met763 on Top2A except Gln778 from Top2B but this does not change of structure of the enzyme because they have the same alfa-helix formations and positions so that it could be predicted that amino acids Gly478, Asp479, Arg503, Met782 and Gln778 on Top2B have similar activity and function with Gly462, Asp463, Arg487, Met763 and Met767 on Top2A. This etoposite could inhibit the activity of the Top2A enzyme at same site.

Tabel 1. BLASTp Top2B Results between Non Human with Top2B Human Templates

 

KLIK DISINI UNTUK INFO LENGKAPNYA

SETIAWAN, Tirta; AMBARSARI, Laksmi; SUMARYADA, Tony Ibnu. STUDI IN SILICO CONVERSE REGION ETOPOSITE BINDING DOMAIN Pada ISOZIM HUMAN DNA TOPOISOMERASE II. CAKRA KIMIA (Indonesian E-Journal of Applied Chemistry), [S.l.], v.4, n.1, p.61 - 70, june 2016. ISSN 2302-7274. Available at: . Date accessed: 09 may 2021.