9SGS
S315G KatG mutant no Heme
Summary for 9SGS
| Entry DOI | 10.2210/pdb9sgs/pdb |
| Related | 9SGL 9SGM 9SGN 9SGO 9SGP 9SGQ 9SGR 9SGT 9SGY |
| EMDB information | 54879 |
| Descriptor | Catalase-peroxidase (1 entity in total) |
| Functional Keywords | catalase, peoxidase, enzyme, heme, metal binding protein |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 2 |
| Total formula weight | 168078.41 |
| Authors | |
| Primary citation | Allport, T.,Chaplin, A.K. Uncovering the structural impact of KatG Ser315 mutations in Mycobacterium tuberculosis via cryo-EM. Protein Sci., 35:e70409-e70409, 2026 Cited by PubMed Abstract: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is responsible for a global health burden affecting over a quarter of the world's population. The increasing prevalence of drug-resistant TB poses a significant threat to current treatment strategies. Isoniazid (INH) is a first-line prodrug used in TB therapy, which requires activation by the catalase-peroxidase enzyme KatG. Upon activation, INH inhibits InhA, thereby disrupting mycolic acid biosynthesis, a crucial process for maintaining Mtb's distinctive, lipid-rich cell wall. The most common naturally occurring resistance-associated mutation in KatG is S315T, though other variants at this position, such as S315G, S315N, S315I, and S315R, have also been reported. In this study, we employ cryo-electron microscopy (cryo-EM) to investigate the structural basis of INH resistance conferred by these KatG variants. We present high-resolution cryo-EM structures that reveal heterogeneity in heme loading among the mutants. Detailed structural analysis highlights alterations in the hydrogen-bonding network and substrate access channel unique to each variant, offering direct comparisons with the wild-type (WT) KatG protein. Our findings provide a molecular explanation for clinical INH resistance and lay the groundwork for the rational design of next-generation anti-TB therapeutics. PubMed: 41432360DOI: 10.1002/pro.70409 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.77 Å) |
Structure validation
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