16S rRNA Methyltransferases as Novel Drug Targets Against Tuberculosis

被引:7
|
作者
Salaikumaran, M. R. [1 ]
Badiger, Veena P. [1 ]
Burra, V. L. S. Prasad [1 ]
机构
[1] KLEF Univ, Ctr Adv Res & Innovat Struct Biol Dis, Vaddeswaram 522502, Andhra Pradesh, India
来源
PROTEIN JOURNAL | 2022年 / 41卷 / 01期
关键词
Methyltransferases; Tuberculosis; SAM-dependent methyltransferases; 16S rRNA; Drug target; ADENOSYL-L-METHIONINE; ESCHERICHIA-COLI; MYCOBACTERIUM-TUBERCULOSIS; CRYSTAL-STRUCTURE; DNA METHYLATION; EPIGENETIC INHERITANCE; STRUCTURAL BASIS; M(5)C967 METHYLTRANSFERASE; P-SITES; RESISTANCE;
D O I
10.1007/s10930-021-10029-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (M.tb) whose natural history traces back to 70,000 years. TB remains a major global health burden. Methylation is a type of post-replication, post-transcriptional and post-translational epi-genetic modification involved in transcription, translation, replication, tissue specific expression, embryonic development, genomic imprinting, genome stability and chromatin structure, protein protein interactions and signal transduction indicating its indispensable role in survival of a pathogen like M.tb. The pathogens use this epigenetic mechanism to develop resistance against certain drug molecules and survive the lethality. Drug resistance has become a major challenge to tackle and also a major concern raised by WHO. Methyltransferases are enzymes that catalyze the methylation of various substrates. None of the current TB targets belong to methyltransferases which provides therapeutic opportunities to develop novel drugs through studying methyltransferases as potential novel targets against TB. Targeting 16S rRNA methyltransferases serves two purposes simultaneously: a) translation inhibition and b) simultaneous elimination of the ability to methylate its substrates hence stopping the emergence of drug resistance strains. There are similar to 40 different rRNA methyltransferases and 13 different 16S rRNA specific methyltransferases which are unexplored and provide a huge opportunity for treatment of TB.
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页码:97 / 130
页数:34
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