Kino

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Crystal structure of KatG

Identifiers
EC number	1.11.1.21
CAS number	9027-73-0
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

KatG is a catalase-peroxidase enzyme that plays a crucial role in the oxidative stress response of certain bacteria, including the Mycobacterium tuberculosis complex. It is a bifunctional enzyme with both catalase and peroxidase activities, which are essential for the detoxification of hydrogen peroxide (H₂O₂) and the activation of the antibiotic isoniazid.

Structure

KatG is a heme-containing enzyme that belongs to the class I peroxidase family. The enzyme is typically a homodimer, with each monomer containing a heme prosthetic group. The structure of KatG is characterized by a conserved heme-binding domain and a unique distal side architecture that facilitates its dual enzymatic activities.

Function

KatG serves two primary functions:

Catalase Activity

KatG catalyzes the decomposition of hydrogen peroxide into water and oxygen, a reaction that is crucial for protecting bacterial cells from oxidative damage:

2 H₂O₂ → 2 H₂O + O₂

This activity helps bacteria survive in hostile environments where reactive oxygen species are present.

Peroxidase Activity

In addition to its catalase function, KatG also exhibits peroxidase activity, which involves the reduction of peroxides using electron donors. This activity is particularly important for the activation of the prodrug isoniazid, a first-line treatment for tuberculosis. KatG converts isoniazid into its active form, which then inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall.

Clinical Significance

Mutations in the KatG gene are a common mechanism of resistance to isoniazid in Mycobacterium tuberculosis. These mutations often result in a loss of catalase-peroxidase activity, rendering the bacteria resistant to the drug. Understanding the structure and function of KatG is therefore critical for developing new strategies to combat drug-resistant tuberculosis.

Research and Applications

Research on KatG has focused on elucidating its structure-function relationships, understanding the mechanisms of drug resistance, and exploring its potential as a target for novel antimicrobial agents. Structural studies using X-ray crystallography have provided insights into the active site configuration and the role of specific amino acids in catalysis and drug activation.

Also see

• Mycobacterium tuberculosis
• Isoniazid
• Catalase
• Peroxidase
• Antibiotic resistance