Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Uncovering the structural impact of KatG Ser315 mutations in Mycobacterium tuberculosis via cryo-EM.
Journal, issue, pages	Protein Sci, Vol. 35, Issue 1, Page e70409, Year 2026
Publish date	Dec 23, 2025
Authors	Thomas Allport / Amanda K Chaplin /
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 ...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.
External links	Protein Sci / PubMed:41432360 / PubMed Central
Methods	EM (single particle)
Resolution	2.27 - 3.0 Å
Structure data	54872 9sgl EMDB-54872, PDB-9sgl: S315T KatG mutant two Heme Method: EM (single particle) / Resolution: 2.27 Å 54873 9sgm EMDB-54873, PDB-9sgm: S315I KatG mutant two Heme Method: EM (single particle) / Resolution: 2.86 Å 54874 9sgn EMDB-54874, PDB-9sgn: S315I KatG mutant no Heme Method: EM (single particle) / Resolution: 3.0 Å 54875 9sgo EMDB-54875, PDB-9sgo: S315N KatG mutant one Heme Method: EM (single particle) / Resolution: 2.74 Å 54876 9sgp EMDB-54876, PDB-9sgp: S315R KatG mutant two Heme Method: EM (single particle) / Resolution: 2.67 Å 54877 9sgq EMDB-54877, PDB-9sgq: S315R KatG mutant one Heme Method: EM (single particle) / Resolution: 2.76 Å 54878 9sgr EMDB-54878, PDB-9sgr: S315N KatG mutant no heme Method: EM (single particle) / Resolution: 2.6 Å 54879 9sgs EMDB-54879, PDB-9sgs: S315G KatG mutant no Heme Method: EM (single particle) / Resolution: 2.77 Å 54880 9sgt EMDB-54880, PDB-9sgt: S315G KatG mutant one Heme Method: EM (single particle) / Resolution: 2.84 Å 54882 9sgy EMDB-54882, PDB-9sgy: S315I KatG mutant one heme Method: EM (single particle) / Resolution: 2.34 Å
Chemicals	ChemComp-HEM: PROTOPORPHYRIN IX CONTAINING FE
Source	mycobacterium tuberculosis (bacteria)
Keywords	METAL BINDING PROTEIN / Catalase / Peoxidase / Enzyme / Heme