rRNK metiltransferaze i njihova uloga u rezistenciji na antibiotike
rRNA methyltransferases and their role in resistance to antibiotics
2010
Autori
Morić, IvanaSavić, Miloje
Ilić-Tomić, Tatjana
Vojnović, Sandra
Bajkić, Sanja
Vasiljević, Branka
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Metiltransferaze (MTaze), koje čine veliku proteinsku superfamiliju, kao donatora metil grupe najčešće koriste S-adenozil-L-metionin (SAM). SAM-zavisne MTaze metiluju nukleinske kiseline (DNK, RNK) i proteine, modulišući tako njihovu aktivnost, funkciju i strukturnu organizaciju. Metilacija G1405 ili A1408 baza u 16S rRNK mikroorganizama koji proizvode aminoglikozide obezbeđuje rezistenciju na sopstvene toksične proizvode. Ovaj mehanizam rezistencije je donedavno bio opisan samo kod proizvođača antibiotika. Od 2003. godine i kod patogenih bakterija beleži se neprestan porast rezistencije na aminoglikozide putem ovog mehanizma, što predstavlja veliku pretnju efikasnoj upotrebi aminoglikozida u kliničkoj praksi. Jedno od mogućih rešenja problema leži u razvoju novih jedinjenja koja bi efikasno delovala na nova mesta u okviru ribozoma. Drugi pristup rešavanju ovog problema uključuje razvoj inhibitora MTaza odgovornih za rezistenciju, sa idejom da se onemogući modifikacija bakterijske rRNK... i na taj način vrati terapeutska efikasnost postojećim aminoglikozidima. Fundamentalna istraživanja vezana za proteinsku ekspresiju, potpuno razumevanje mehanizma rezistencije kao i razrešenje tercijarne strukture proteina su neophodan preduslov za primenu inhibitora 16S rRNK MTaza u medicini.
Methyltransferases (MTases), a large protein superfamily, commonly use S-adenosyl-L-methionine (SAM) as the methyl group donor. SAM-dependant MTases methylate both nucleic acids (DNA, RNA) and proteins, and thus modulate their activity, function and folding. Methylation of G1405 or A1408 nucleotides of 16S rRNA in aminoglycoside-producing microorganisms confers the resistance to their own toxic product(s). This mechanism of resistance has been considered as unique to antibiotics producers until recently. Since 2003, methylation of 16S rRNA as a mechanism of resistance is increasingly emerging in pathogenic bacteria. This represents a major threat towards the usefulness of aminoglycosides in the clinical practice. A potential solution to the problem involves the design of novel compounds that would act against new ribosomal targets. The second approach to the issue includes the development of resistance MTases' inhibitors, with the idea to prevent them from modifying the bacterial rRNA,... and thus reinstate the therapeutic power of existing aminoglycosides. As the latter approach has considerable potential, it is obvious that fundamental research related to protein expression, in-depth understanding of the mechanism of action and resolving a tertiary structure of 16S rRNAs MTases are prerequisites for application in medicine.
Ključne reči:
ribozom / rezistencija / metiltransferaze / aminoglikozidi / ribosome / resistance / methyltransferases / aminoglycosidesIzvor:
Journal of Medical Biochemistry, 2010, 29, 3, 165-174Izdavač:
- Društvo medicinskih biohemičara Srbije, Beograd i Versita
Finansiranje / projekti:
- Ekspresija i regulacija farmaceutski značajnih gena u mikroorganizmima (RS-MESTD-MPN2006-2010-143056)
DOI: 10.2478/v10011-010-0030-y
ISSN: 1452-8258
WoS: 000280477800006
Scopus: 2-s2.0-77955233469
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Morić, Ivana AU - Savić, Miloje AU - Ilić-Tomić, Tatjana AU - Vojnović, Sandra AU - Bajkić, Sanja AU - Vasiljević, Branka PY - 2010 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/455 AB - Metiltransferaze (MTaze), koje čine veliku proteinsku superfamiliju, kao donatora metil grupe najčešće koriste S-adenozil-L-metionin (SAM). SAM-zavisne MTaze metiluju nukleinske kiseline (DNK, RNK) i proteine, modulišući tako njihovu aktivnost, funkciju i strukturnu organizaciju. Metilacija G1405 ili A1408 baza u 16S rRNK mikroorganizama koji proizvode aminoglikozide obezbeđuje rezistenciju na sopstvene toksične proizvode. Ovaj mehanizam rezistencije je donedavno bio opisan samo kod proizvođača antibiotika. Od 2003. godine i kod patogenih bakterija beleži se neprestan porast rezistencije na aminoglikozide putem ovog mehanizma, što predstavlja veliku pretnju efikasnoj upotrebi aminoglikozida u kliničkoj praksi. Jedno od mogućih rešenja problema leži u razvoju novih jedinjenja koja bi efikasno delovala na nova mesta u okviru ribozoma. Drugi pristup rešavanju ovog problema uključuje razvoj inhibitora MTaza odgovornih za rezistenciju, sa idejom da se onemogući modifikacija bakterijske rRNK i na taj način vrati terapeutska efikasnost postojećim aminoglikozidima. Fundamentalna istraživanja vezana za proteinsku ekspresiju, potpuno razumevanje mehanizma rezistencije kao i razrešenje tercijarne strukture proteina su neophodan preduslov za primenu inhibitora 16S rRNK MTaza u medicini. AB - Methyltransferases (MTases), a large protein superfamily, commonly use S-adenosyl-L-methionine (SAM) as the methyl group donor. SAM-dependant MTases methylate both nucleic acids (DNA, RNA) and proteins, and thus modulate their activity, function and folding. Methylation of G1405 or A1408 nucleotides of 16S rRNA in aminoglycoside-producing microorganisms confers the resistance to their own toxic product(s). This mechanism of resistance has been considered as unique to antibiotics producers until recently. Since 2003, methylation of 16S rRNA as a mechanism of resistance is increasingly emerging in pathogenic bacteria. This represents a major threat towards the usefulness of aminoglycosides in the clinical practice. A potential solution to the problem involves the design of novel compounds that would act against new ribosomal targets. The second approach to the issue includes the development of resistance MTases' inhibitors, with the idea to prevent them from modifying the bacterial rRNA, and thus reinstate the therapeutic power of existing aminoglycosides. As the latter approach has considerable potential, it is obvious that fundamental research related to protein expression, in-depth understanding of the mechanism of action and resolving a tertiary structure of 16S rRNAs MTases are prerequisites for application in medicine. PB - Društvo medicinskih biohemičara Srbije, Beograd i Versita T2 - Journal of Medical Biochemistry T1 - rRNK metiltransferaze i njihova uloga u rezistenciji na antibiotike T1 - rRNA methyltransferases and their role in resistance to antibiotics EP - 174 IS - 3 SP - 165 VL - 29 DO - 10.2478/v10011-010-0030-y ER -
@article{ author = "Morić, Ivana and Savić, Miloje and Ilić-Tomić, Tatjana and Vojnović, Sandra and Bajkić, Sanja and Vasiljević, Branka", year = "2010", abstract = "Metiltransferaze (MTaze), koje čine veliku proteinsku superfamiliju, kao donatora metil grupe najčešće koriste S-adenozil-L-metionin (SAM). SAM-zavisne MTaze metiluju nukleinske kiseline (DNK, RNK) i proteine, modulišući tako njihovu aktivnost, funkciju i strukturnu organizaciju. Metilacija G1405 ili A1408 baza u 16S rRNK mikroorganizama koji proizvode aminoglikozide obezbeđuje rezistenciju na sopstvene toksične proizvode. Ovaj mehanizam rezistencije je donedavno bio opisan samo kod proizvođača antibiotika. Od 2003. godine i kod patogenih bakterija beleži se neprestan porast rezistencije na aminoglikozide putem ovog mehanizma, što predstavlja veliku pretnju efikasnoj upotrebi aminoglikozida u kliničkoj praksi. Jedno od mogućih rešenja problema leži u razvoju novih jedinjenja koja bi efikasno delovala na nova mesta u okviru ribozoma. Drugi pristup rešavanju ovog problema uključuje razvoj inhibitora MTaza odgovornih za rezistenciju, sa idejom da se onemogući modifikacija bakterijske rRNK i na taj način vrati terapeutska efikasnost postojećim aminoglikozidima. Fundamentalna istraživanja vezana za proteinsku ekspresiju, potpuno razumevanje mehanizma rezistencije kao i razrešenje tercijarne strukture proteina su neophodan preduslov za primenu inhibitora 16S rRNK MTaza u medicini., Methyltransferases (MTases), a large protein superfamily, commonly use S-adenosyl-L-methionine (SAM) as the methyl group donor. SAM-dependant MTases methylate both nucleic acids (DNA, RNA) and proteins, and thus modulate their activity, function and folding. Methylation of G1405 or A1408 nucleotides of 16S rRNA in aminoglycoside-producing microorganisms confers the resistance to their own toxic product(s). This mechanism of resistance has been considered as unique to antibiotics producers until recently. Since 2003, methylation of 16S rRNA as a mechanism of resistance is increasingly emerging in pathogenic bacteria. This represents a major threat towards the usefulness of aminoglycosides in the clinical practice. A potential solution to the problem involves the design of novel compounds that would act against new ribosomal targets. The second approach to the issue includes the development of resistance MTases' inhibitors, with the idea to prevent them from modifying the bacterial rRNA, and thus reinstate the therapeutic power of existing aminoglycosides. As the latter approach has considerable potential, it is obvious that fundamental research related to protein expression, in-depth understanding of the mechanism of action and resolving a tertiary structure of 16S rRNAs MTases are prerequisites for application in medicine.", publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita", journal = "Journal of Medical Biochemistry", title = "rRNK metiltransferaze i njihova uloga u rezistenciji na antibiotike, rRNA methyltransferases and their role in resistance to antibiotics", pages = "174-165", number = "3", volume = "29", doi = "10.2478/v10011-010-0030-y" }
Morić, I., Savić, M., Ilić-Tomić, T., Vojnović, S., Bajkić, S.,& Vasiljević, B.. (2010). rRNK metiltransferaze i njihova uloga u rezistenciji na antibiotike. in Journal of Medical Biochemistry Društvo medicinskih biohemičara Srbije, Beograd i Versita., 29(3), 165-174. https://doi.org/10.2478/v10011-010-0030-y
Morić I, Savić M, Ilić-Tomić T, Vojnović S, Bajkić S, Vasiljević B. rRNK metiltransferaze i njihova uloga u rezistenciji na antibiotike. in Journal of Medical Biochemistry. 2010;29(3):165-174. doi:10.2478/v10011-010-0030-y .
Morić, Ivana, Savić, Miloje, Ilić-Tomić, Tatjana, Vojnović, Sandra, Bajkić, Sanja, Vasiljević, Branka, "rRNK metiltransferaze i njihova uloga u rezistenciji na antibiotike" in Journal of Medical Biochemistry, 29, no. 3 (2010):165-174, https://doi.org/10.2478/v10011-010-0030-y . .