DFT study on the effect of proximal residues on the Mycobacterium tuberculosis catalase-peroxidase (katG) heme compound I intermediate and its bonding interaction with isoniazid

2019 ◽  
Vol 21 (30) ◽  
pp. 16515-16525 ◽  
Author(s):  
Yves Ira A. Reyes ◽  
Francisco C. Franco
Keyword(s):  
Electron Transfer ◽  
Mycobacterium Tuberculosis ◽  
Dft Study ◽  
Porphyrin Ring ◽  
Compound I ◽  
Bonding Interaction ◽  
Catalase Peroxidase ◽  
Radical Character

In M. tb. katG heme CpdI intermediate, an electron transfer from the π-orbital of the residue, Trp321, to the a2u-orbital of porphyrin ring, results in a radical character for Trp321, resulting in a stronger H-bonding interaction with INH.

scholarly journals Using cryo-EM to understand antimycobacterial resistance in the catalase-peroxidase (KatG) from Mycobacterium tuberculosis

Structure ◽  
2021 ◽  
Author(s):  
Asma Munir ◽  
Michael T. Wilson ◽  
Steven W. Hardwick ◽  
Dimitri Y. Chirgadze ◽  
Jonathan A.R. Worrall ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Catalase Peroxidase

Significance of catalase-peroxidase (KatG) mutations in mediating isoniazid resistance in clinical strains of Mycobacterium tuberculosis

2018 ◽  
Vol 15 ◽  
pp. 111-120 ◽  
Author(s):  
Ameeruddin Nusrath Unissa ◽  
George Priya Doss C ◽  
Thirumal Kumar ◽  
Swathi Sukumar ◽  
Appisetty Ramya Lakshmi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Isoniazid Resistance ◽  
Clinical Strains ◽  
Catalase Peroxidase

scholarly journals Characterization of Mycobacterium tuberculosis Isolates from Patients in Houston, Texas, by Spoligotyping

2000 ◽  
Vol 38 (2) ◽  
pp. 669-676 ◽  
Author(s):  
Hanna Soini ◽  
Xi Pan ◽  
Amol Amin ◽  
Edward A. Graviss ◽  
Anees Siddiqui ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Population Based ◽  
Nucleotide Polymorphisms ◽  
Genetic Groups ◽  
Tuberculosis Epidemiology ◽  
New Information ◽  
Catalase Peroxidase ◽  
A Subunit ◽  
Group 2 ◽  
Group 1

Mycobacterium tuberculosis isolates (n= 1,429) from 1,283 patients collected as part of an ongoing population-based tuberculosis epidemiology study in Houston, Texas, were analyzed by spoligotyping and IS6110 profiling. The isolates were also assigned to one of three major genetic groups on the basis of nucleotide polymorphisms located at codons 463 and 95 in the genes (katG and gyrA) encoding catalase-peroxidase and the A subunit of DNA gyrase, respectively. A total of 225 spoligotypes were identified in the 1,429 isolates. There were 54 spoligotypes identified among 713 isolates (n= 623 patients) assigned to 73 IS6110 clusters. In addition, among 716 isolates (n = 660 patients) with unique IS6110 profiles, 200 spoligotypes were identified. No changes were observed either in the IS6110 profile or in the spoligotype for the 281 isolates collected sequentially from 133 patients. Five instances in which isolates with slightly different spoligotypes had the same IS6110 profile were identified, suggesting that in rare cases isolates with different spoligotypes can be clonally related. Spoligotypes correlated extremely well with major genetic group designations. Only three very similar spoligotypes were shared by isolates from genetic groups 2 and 3, and none was shared by group 1 and group 2 organisms or by group 1 and group 3 organisms. All organisms belonging to genetic groups 2 and 3 failed to hybridize with spacer probes 33 to 36. Taken together, the results support the existence of three distinct genetic groups of M. tuberculosis organisms and provide new information about the relationship between IS6110 profiles, spoligotypes, and major genetic groups of M. tuberculosis.

Small Reorganization Energy for Ligand-Centered Electron-Transfer Reduction of Compound I to Compound II in a Heme Model Study

2019 ◽  
Vol 58 (13) ◽  
pp. 8263-8266 ◽  
Author(s):  
Nami Fukui ◽  
Xiao-Xi Li ◽  
Wonwoo Nam ◽  
Shunichi Fukuzumi ◽  
Hiroshi Fujii
Keyword(s):  
Electron Transfer ◽  
Reorganization Energy ◽  
Compound I ◽  
Model Study ◽  
Compound Ii

scholarly journals ethA, inhA, and katG Loci of Ethionamide-Resistant Clinical Mycobacterium tuberculosis Isolates

2003 ◽  
Vol 47 (12) ◽  
pp. 3799-3805 ◽  
Author(s):  
Glenn P. Morlock ◽  
Beverly Metchock ◽  
David Sikes ◽  
Jack T. Crawford ◽  
Robert C. Cooksey
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Structural Gene ◽  
Single Point ◽  
Resistance Mechanism ◽  
Structural Analog ◽  
Mycolic Acid ◽  
Single Point Mutation ◽  
Structural Genes ◽  
Resistance Mutations ◽  
Catalase Peroxidase

ABSTRACT Ethionamide (ETH) is a structural analog of the antituberculosis drug isoniazid (INH). Both of these drugs target InhA, an enzyme involved in mycolic acid biosynthesis. INH requires catalase-peroxidase (KatG) activation, and mutations in katG are a major INH resistance mechanism. Recently an enzyme (EthA) capable of activating ETH has been identified. We sequenced the entire ethA structural gene of 41 ETH-resistant Mycobacterium tuberculosis isolates. We also sequenced two regions of inhA and all or part of katG. The MICs of ETH and INH were determined in order to associate the mutations identified with a resistance phenotype. Fifteen isolates were found to possess ethA mutations, for all of which the ETH MICs were ≥50 μg/ml. The ethA mutations were all different, previously unreported, and distributed throughout the gene. In eight of the isolates, a missense mutation in the inhA structural gene occurred. The ETH MICs for seven of the InhA mutants were ≥100 μg/ml, and these isolates were also resistant to ≥8 μg of INH per ml. Only a single point mutation in the inhA promoter was identified in 14 isolates. A katG mutation occurred in 15 isolates, for which the INH MICs for all but 1 were ≥32 μg/ml. As expected, we found no association between katG mutation and the level of ETH resistance. Mutations within the ethA and inhA structural genes were associated with relatively high levels of ETH resistance. Approximately 76% of isolates resistant to ≥50 μg of ETH per ml had such mutations.

scholarly journals Requirements for Nitric Oxide Generation from Isoniazid Activation In Vitro and Inhibition of Mycobacterial Respiration In Vivo

2004 ◽  
Vol 186 (16) ◽  
pp. 5427-5431 ◽  
Author(s):  
Graham S. Timmins ◽  
Sharon Master ◽  
Frank Rusnak ◽  
Vojo Deretic
Keyword(s):  
Nitric Oxide ◽  
Mycobacterium Tuberculosis ◽  
Reactive Species ◽  
Front Line ◽  
Respiratory Enzymes ◽  
Catalase Peroxidase ◽  
Oxidative Activation

ABSTRACT Isoniazid (INH), a front-line antituberculosis agent, is activated by mycobacterial catalase-peroxidase KatG, converting INH into bactericidal reactive species. Here we investigated the requirements and the pathway of nitric oxide (NO˙) generation during oxidative activation of INH by Mycobacterium tuberculosis KatG in vitro. We also provide in vivo evidence that INH-derived NO˙ can inhibit key mycobacterial respiratory enzymes, which may contribute to the overall antimycobacterial action of INH.

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