Cytochrome P450 130A1 (CYP130) (CYP130)

Cytochrome P450 130A1 (CYP130) is a heme-thiolate monooxygenase enzyme found in Mycobacterium tuberculosis, the pathogen responsible for tuberculosis [1, 3]. It is one of twenty cytochrome P450 enzymes encoded by the M. tuberculosis genome and is of particular interest because it is absent in the Mycobacterium bovis strain [2, 5]. This absence suggests that CYP130 may play a specialized role in the virulence and infectivity of the bacterium specifically within human hosts [3, 5]. Although its natural physiological substrate has not yet been definitively identified, the enzyme is known to bind various small molecules, including antifungal azole drugs [1, 5]. Drugs such as econazole and clotrimazole act as Type II inhibitors by coordinating to the heme iron, which triggers a significant conformational change from an open to a closed state [2, 5]. The gene encoding CYP130, Rv1256c, is located in a potential operon with the Rv1258c efflux pump, suggesting a possible link to drug resistance mechanisms [5]. As a result, CYP130 is considered a promising therapeutic target for the development of novel anti-tubercular agents, especially against multi-drug resistant strains [1, 4]. Research into its structure and inhibition continues to provide insights into the metabolic vulnerabilities of M. tuberculosis [3, 4].

Other names

CYP130A1Rv1256cCytochrome P450 130

Inhibition of enzyme activity through Type II binding, where the inhibitor coordinates directly to the heme iron atom, displacing the axial water ligand and preventing the binding of the natural substrate [2, 5].