Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design
Recent studies have reported the β-ketoacyl-acyl carrier protein KasA as a druggable target for Mycobacterium tuberculosis. This review summarizes the current status of major classes of KasA inhibitors with an emphasis on significant contributions from structure-based design methods leveraging X-ray...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1008213/full |
| _version_ | 1818050266101972992 |
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| author | Reshma S. Rudraraju Samer S. Daher Ricardo Gallardo-Macias Xin Wang Matthew B. Neiditch Joel S. Freundlich Joel S. Freundlich |
| author_facet | Reshma S. Rudraraju Samer S. Daher Ricardo Gallardo-Macias Xin Wang Matthew B. Neiditch Joel S. Freundlich Joel S. Freundlich |
| author_sort | Reshma S. Rudraraju |
| collection | DOAJ |
| description | Recent studies have reported the β-ketoacyl-acyl carrier protein KasA as a druggable target for Mycobacterium tuberculosis. This review summarizes the current status of major classes of KasA inhibitors with an emphasis on significant contributions from structure-based design methods leveraging X-ray crystal structures of KasA alone and in complex with inhibitors. The issues addressed within each inhibitor class are discussed while detailing the characterized interactions with KasA and structure-activity relationships. A critical analysis of these findings should lay the foundation for new KasA inhibitors to study the basic biology of M. tuberculosis and to form the basis of new antitubercular molecules of clinical significance with activity against drug-sensitive and drug-resistant infections. |
| first_indexed | 2024-12-10T10:50:44Z |
| format | Article |
| id | doaj.art-3dc96799c34046d29477f7a07e79ea77 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-10T10:50:44Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-3dc96799c34046d29477f7a07e79ea772022-12-22T01:52:01ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-09-011210.3389/fcimb.2022.10082131008213Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor designReshma S. Rudraraju0Samer S. Daher1Ricardo Gallardo-Macias2Xin Wang3Matthew B. Neiditch4Joel S. Freundlich5Joel S. Freundlich6Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, NJ, United StatesDepartment of Pharmacology, Physiology, and Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ, United StatesDepartment of Pharmacology, Physiology, and Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ, United StatesDepartment of Immunology and Infectious Diseases, Harvard University T.H. Chan School of Public Health, Boston, MA, United StatesDepartment of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, NJ, United StatesDepartment of Pharmacology, Physiology, and Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ, United StatesDepartment of Medicine, Center for Emerging and Re-emerging Pathogens, New Jersey Medical School, Rutgers University, Newark, NJ, United StatesRecent studies have reported the β-ketoacyl-acyl carrier protein KasA as a druggable target for Mycobacterium tuberculosis. This review summarizes the current status of major classes of KasA inhibitors with an emphasis on significant contributions from structure-based design methods leveraging X-ray crystal structures of KasA alone and in complex with inhibitors. The issues addressed within each inhibitor class are discussed while detailing the characterized interactions with KasA and structure-activity relationships. A critical analysis of these findings should lay the foundation for new KasA inhibitors to study the basic biology of M. tuberculosis and to form the basis of new antitubercular molecules of clinical significance with activity against drug-sensitive and drug-resistant infections.https://www.frontiersin.org/articles/10.3389/fcimb.2022.1008213/fullmycobacterium tuberculosisKasAβ-ketoacyl synthasestructure-based drug discoverymedicinal chemistry |
| spellingShingle | Reshma S. Rudraraju Samer S. Daher Ricardo Gallardo-Macias Xin Wang Matthew B. Neiditch Joel S. Freundlich Joel S. Freundlich Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design Frontiers in Cellular and Infection Microbiology mycobacterium tuberculosis KasA β-ketoacyl synthase structure-based drug discovery medicinal chemistry |
| title | Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design |
| title_full | Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design |
| title_fullStr | Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design |
| title_full_unstemmed | Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design |
| title_short | Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design |
| title_sort | mycobacterium tuberculosis kasa as a drug target structure based inhibitor design |
| topic | mycobacterium tuberculosis KasA β-ketoacyl synthase structure-based drug discovery medicinal chemistry |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1008213/full |
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