Biosynthesis of Galactan in <i>Mycobacterium tuberculosis</i> as a Viable TB Drug Target?
While target-based drug design has proved successful in several therapeutic areas, this approach has not yet provided compelling outcomes in the field of antibacterial agents. This statement remains especially true for the development of novel therapeutic interventions against tuberculosis, an infec...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-01-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/9/1/20 |
| _version_ | 1818528630193520640 |
|---|---|
| author | Zuzana Konyariková Karin Savková Stanislav Kozmon Katarína Mikušová |
| author_facet | Zuzana Konyariková Karin Savková Stanislav Kozmon Katarína Mikušová |
| author_sort | Zuzana Konyariková |
| collection | DOAJ |
| description | While target-based drug design has proved successful in several therapeutic areas, this approach has not yet provided compelling outcomes in the field of antibacterial agents. This statement remains especially true for the development of novel therapeutic interventions against tuberculosis, an infectious disease that is among the top ten leading causes of death globally. Mycobacterial galactan is an important component of the protective cell wall core of the tuberculosis pathogen and it could provide a promising target for the design of new drugs. In this review, we summarize the current knowledge on galactan biosynthesis in <i>Mycobacterium tuberculosis</i>, including landmark findings that led to the discovery and understanding of three key enzymes in this pathway: UDP-galactose mutase, and galactofuranosyl transferases GlfT1 and GlfT2. Moreover, we recapitulate the efforts aimed at their inhibition. The predicted common transition states of the three enzymes provide the lucrative possibility of multitargeting in pharmaceutical development, a favourable property in the mitigation of drug resistance. We believe that a tight interplay between target-based computational approaches and experimental methods will result in the development of original inhibitors that could serve as the basis of a new generation of drugs against tuberculosis. |
| first_indexed | 2024-12-11T06:52:29Z |
| format | Article |
| id | doaj.art-4bda942a627a48d2b9066c344f647824 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-12-11T06:52:29Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-4bda942a627a48d2b9066c344f6478242022-12-22T01:16:51ZengMDPI AGAntibiotics2079-63822020-01-01912010.3390/antibiotics9010020antibiotics9010020Biosynthesis of Galactan in <i>Mycobacterium tuberculosis</i> as a Viable TB Drug Target?Zuzana Konyariková0Karin Savková1Stanislav Kozmon2Katarína Mikušová3Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina, Ilkovičova 6, 84215 Bratislava, SlovakiaDepartment of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina, Ilkovičova 6, 84215 Bratislava, SlovakiaInstitute of Chemistry, Slovak Academy of Sciences, Dúbravská Cesta 9, 84538 Bratislava, SlovakiaDepartment of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina, Ilkovičova 6, 84215 Bratislava, SlovakiaWhile target-based drug design has proved successful in several therapeutic areas, this approach has not yet provided compelling outcomes in the field of antibacterial agents. This statement remains especially true for the development of novel therapeutic interventions against tuberculosis, an infectious disease that is among the top ten leading causes of death globally. Mycobacterial galactan is an important component of the protective cell wall core of the tuberculosis pathogen and it could provide a promising target for the design of new drugs. In this review, we summarize the current knowledge on galactan biosynthesis in <i>Mycobacterium tuberculosis</i>, including landmark findings that led to the discovery and understanding of three key enzymes in this pathway: UDP-galactose mutase, and galactofuranosyl transferases GlfT1 and GlfT2. Moreover, we recapitulate the efforts aimed at their inhibition. The predicted common transition states of the three enzymes provide the lucrative possibility of multitargeting in pharmaceutical development, a favourable property in the mitigation of drug resistance. We believe that a tight interplay between target-based computational approaches and experimental methods will result in the development of original inhibitors that could serve as the basis of a new generation of drugs against tuberculosis.https://www.mdpi.com/2079-6382/9/1/20udp-galactose mutasegalactofuranosyl transferaseglft1glft2cell walldrug design |
| spellingShingle | Zuzana Konyariková Karin Savková Stanislav Kozmon Katarína Mikušová Biosynthesis of Galactan in <i>Mycobacterium tuberculosis</i> as a Viable TB Drug Target? Antibiotics udp-galactose mutase galactofuranosyl transferase glft1 glft2 cell wall drug design |
| title | Biosynthesis of Galactan in <i>Mycobacterium tuberculosis</i> as a Viable TB Drug Target? |
| title_full | Biosynthesis of Galactan in <i>Mycobacterium tuberculosis</i> as a Viable TB Drug Target? |
| title_fullStr | Biosynthesis of Galactan in <i>Mycobacterium tuberculosis</i> as a Viable TB Drug Target? |
| title_full_unstemmed | Biosynthesis of Galactan in <i>Mycobacterium tuberculosis</i> as a Viable TB Drug Target? |
| title_short | Biosynthesis of Galactan in <i>Mycobacterium tuberculosis</i> as a Viable TB Drug Target? |
| title_sort | biosynthesis of galactan in i mycobacterium tuberculosis i as a viable tb drug target |
| topic | udp-galactose mutase galactofuranosyl transferase glft1 glft2 cell wall drug design |
| url | https://www.mdpi.com/2079-6382/9/1/20 |
| work_keys_str_mv | AT zuzanakonyarikova biosynthesisofgalactaninimycobacteriumtuberculosisiasaviabletbdrugtarget AT karinsavkova biosynthesisofgalactaninimycobacteriumtuberculosisiasaviabletbdrugtarget AT stanislavkozmon biosynthesisofgalactaninimycobacteriumtuberculosisiasaviabletbdrugtarget AT katarinamikusova biosynthesisofgalactaninimycobacteriumtuberculosisiasaviabletbdrugtarget |