#TITLE_ALTERNATIVE#

• Main Author: NIM : 20716019, JUNAIDIN
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/28360
• Institution: Institut Teknologi Bandung

Tuberculosis (TB) is one of the many known diseases that infect humans caused by <br /> <br /> M. tuberculosis. The incidence of TB began to show a pattern of resistance known as <br /> <br /> Multidrug Resistant Tuberculosis (MDR-TB) mainly for first-line drugs, one of them <br /> <br /> isoniazid (INH). In various studies showing patients with MDR-TB resistant INH have <br /> <br /> mutation at katG gene in the region S315T that play a role in coding enzyme catalase <br /> <br /> peroxidase (CP) from M. tuberculosis. The purpose of this study was to examine the <br /> <br /> relationship between the mutation of katG gene with resistance occurring to INH by <br /> <br /> in silico studies. In this study, we modeled resistant mutants of enzyme CP from katG <br /> <br /> gene S315T with humology modeling method using by I-Tasser <br /> <br /> ® <br /> <br /> , Raptor-X <br /> <br /> ® <br /> <br /> , and <br /> <br /> Swiss-Model <br /> <br /> ® <br /> <br /> . Molecular geometry-optimized structure of INH using by DFT- <br /> <br /> B3LYP method with basis set 6-31G. Docking of CP wildtype and mutants S315T <br /> <br /> with AutodockTools that followed by simulation MD. Result of evaluation and <br /> <br /> optimization model of the enzyme CP mutant S315T obtained the best model that is <br /> <br /> model produced by Swiss-Model®. Docking of the enzyme CP wildtype and mutant <br /> <br /> S315T show different feature interaction on the active site of enzyme as the center of <br /> <br /> catalysis. This results characterized by a decrease affinity of INH that occurring on the <br /> <br /> mutant S315T and results interaction pose of INH from mutant S315T that leads out <br /> <br /> of the catalysis region. Models of docking on wildtype showed INH molecules <br /> <br /> interacting with the main residue of Asp137 plays a role in activating INH into active <br /> <br /> form. The plot analysis of RMSD and RMSF during simulation of molecular dynamics <br /> <br /> showed the complex of both enzymes was quite stable and mutant S315T were known <br /> <br /> to have the highest flexibility in the 315-318 amino acid residues compared to <br /> <br /> wildtype. The results of in silico study show that resistance to INH has a relationship <br /> <br /> with the mutation katG gene in the region S315T. Mutations occurring in the S315T <br /> <br /> katG gene allow for active site changes recommended as a site for INH activation. <br />