{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:43:22Z","timestamp":1791431002434,"version":"4.3.3"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In order to probe the structure and function of the mycobacterial catalase-peroxidase enzyme (KatG), we employed a genetic approach using dominant-negative analysis of\n            <jats:italic>katG<\/jats:italic>\n            merodiploids. Transformation of\n            <jats:italic>Mycobacterium bovis<\/jats:italic>\n            BCG with various\n            <jats:italic>katG<\/jats:italic>\n            point mutants (expressed from low-copy-number plasmids) resulted in reductions in peroxidase and catalase activities as measured in cell extracts. These reductions in enzymatic activity usually correlated with increased resistance to the antituberculosis drug isoniazid (INH). However, for the N138S\n            <jats:italic>trans<\/jats:italic>\n            -dominant mutant, the catalase-peroxidase activity was significantly decreased while the sensitivity to INH was retained.\n            <jats:italic>trans<\/jats:italic>\n            -dominance required\n            <jats:italic>katG<\/jats:italic>\n            expression from multicopy plasmids and could not be demonstrated with\n            <jats:italic>katG<\/jats:italic>\n            mutants integrated elsewhere on the wild-type\n            <jats:italic>M. bovis<\/jats:italic>\n            BCG chromosome. Reversal of the mutant phenotype through plasmid exchange suggested the catalase-peroxidase deficiency occurred at the protein level and that INH resistance was not due to a second site mutation(s). Electrophoretic analysis of KatG proteins from the\n            <jats:italic>trans<\/jats:italic>\n            -dominant mutants showed a reduction in KatG dimers compared to WT and formation of heterodimers with reduced activity. The mutants responsible for these defects cluster around proposed active site residues: N138S, T275P, S315T, and D381G. In an attempt to identify mutants that might delimit the region(s) of KatG involved in subunit interactions, C-terminal truncations were constructed (with and without the D381G dominant-negative mutation). None of the C-terminal deletions were able to complement a \u0394\n            <jats:italic>katG<\/jats:italic>\n            strain, nor could they cause a dominant-negative effect on the WT. Taken together, these results suggest an intricate association between the amino- and carboxy-terminal regions of KatG and may be consistent with a domain-swapping mechanism for KatG dimer formation.\n          <\/jats:p>","DOI":"10.1128\/aac.47.1.188-195.2003","type":"journal-article","created":{"date-parts":[[2002,12,24]],"date-time":"2002-12-24T04:39:08Z","timestamp":1040704748000},"page":"188-195","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Exploring the Structure and Function of the Mycobacterial KatG Protein Using\n            <i>trans<\/i>\n            -Dominant Mutants"],"prefix":"10.1128","volume":"47","author":[{"given":"Joseph A.","family":"DeVito","sequence":"first","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 19880"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheldon","family":"Morris","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 19880"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8284673"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50881-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1450093"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.7.2172"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"6271","DOI":"10.1093\/emboj\/18.22.6271","volume":"18","year":"1999","unstructured":"Crane, B. 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