Inhibition of a Mycobacterium tuberculosis β-Ketoacyl ACP Synthase by Isoniazid

Abstract

Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the treatment of tuberculosis, its molecular target has remained elusive. In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50. A protein species purified from INH-treated Mycobacterium tuberculosis was shown to consist of a covalent complex of INH, AcpM, and a β-ketoacyl acyl carrier protein synthase, KasA. Amino acid–altering mutations in the KasA protein were identified in INH-resistant patient isolates that lacked other mutations associated with resistance to this drug.

Keywords

IsoniazidMycobacterium tuberculosisMicrobiologyIsonicotinic acidHydrazideTuberculosisBiochemistryChemistryBiologyMedicine

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Publication Info

Year: 1998
Type: article
Volume: 280
Issue: 5369
Pages: 1607-1610
Citations: 394
Access: Closed

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APA Style

                            
                                
                                    Khisimuzi Mdluli, 
                                
                                    Richard A. Slayden, 
                                
                                    Ya-Qi Zhu
                                
                                et al.
                            
                            (1998). 
                            Inhibition of a <i>Mycobacterium tuberculosis</i> β-Ketoacyl ACP Synthase by Isoniazid. 
                            Science
                            , 280
                            (5369)
                            , 1607-1610.
                            https://doi.org/10.1126/science.280.5369.1607
                        

Identifiers

DOI: 10.1126/science.280.5369.1607

Inhibition of a <i>Mycobacterium tuberculosis</i> β-Ketoacyl ACP Synthase by Isoniazid