Cargando…
The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms
Sulfolipid-1 (SL-1) is located in the Mycobacterium tuberculosis (M. tb) cell wall, and is essential for pathogen virulence and intracellular growth. Multiple proteins (e.g., Pks2, FadD23, PapA1, and MmpL8) in the SL-1 synthesis pathway can be treated as drug targets, but, to date, their structures...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989471/ https://www.ncbi.nlm.nih.gov/pubmed/36896429 http://dx.doi.org/10.3389/fmicb.2023.1090534 |
_version_ | 1784901774338949120 |
---|---|
author | Yan, Mengrong Cao, Lin Zhao, Li Zhou, Weihong Liu, Xiang Zhang, Wei Rao, Zihe |
author_facet | Yan, Mengrong Cao, Lin Zhao, Li Zhou, Weihong Liu, Xiang Zhang, Wei Rao, Zihe |
author_sort | Yan, Mengrong |
collection | PubMed |
description | Sulfolipid-1 (SL-1) is located in the Mycobacterium tuberculosis (M. tb) cell wall, and is essential for pathogen virulence and intracellular growth. Multiple proteins (e.g., Pks2, FadD23, PapA1, and MmpL8) in the SL-1 synthesis pathway can be treated as drug targets, but, to date, their structures have not been solved. The crystal structures of FadD23 bound to ATP or hexadecanoyl adenylate was determined in this study. We have also investigated long-chain saturated fatty acids as biological substrates of FadD23 through structural, biological, and chemical analyses. The mutation at the active site of FadD23 greatly influences enzymatic activity. Meanwhile, the FadD23 N-terminal domain alone cannot bind palmitic acid without C-terminal domain facilitation since it is almost inactive after removing the C-terminal domain. FadD23 is the first protein in the SL-1 synthesis pathway whose structure has been solved. These results reveal the importance of the C-terminal domain in the catalytic mechanism. |
format | Online Article Text |
id | pubmed-9989471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99894712023-03-08 The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms Yan, Mengrong Cao, Lin Zhao, Li Zhou, Weihong Liu, Xiang Zhang, Wei Rao, Zihe Front Microbiol Microbiology Sulfolipid-1 (SL-1) is located in the Mycobacterium tuberculosis (M. tb) cell wall, and is essential for pathogen virulence and intracellular growth. Multiple proteins (e.g., Pks2, FadD23, PapA1, and MmpL8) in the SL-1 synthesis pathway can be treated as drug targets, but, to date, their structures have not been solved. The crystal structures of FadD23 bound to ATP or hexadecanoyl adenylate was determined in this study. We have also investigated long-chain saturated fatty acids as biological substrates of FadD23 through structural, biological, and chemical analyses. The mutation at the active site of FadD23 greatly influences enzymatic activity. Meanwhile, the FadD23 N-terminal domain alone cannot bind palmitic acid without C-terminal domain facilitation since it is almost inactive after removing the C-terminal domain. FadD23 is the first protein in the SL-1 synthesis pathway whose structure has been solved. These results reveal the importance of the C-terminal domain in the catalytic mechanism. Frontiers Media S.A. 2023-02-21 /pmc/articles/PMC9989471/ /pubmed/36896429 http://dx.doi.org/10.3389/fmicb.2023.1090534 Text en Copyright © 2023 Yan, Cao, Zhao, Zhou, Liu, Zhang and Rao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Yan, Mengrong Cao, Lin Zhao, Li Zhou, Weihong Liu, Xiang Zhang, Wei Rao, Zihe The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms |
title | The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms |
title_full | The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms |
title_fullStr | The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms |
title_full_unstemmed | The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms |
title_short | The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms |
title_sort | key roles of mycobacterium tuberculosis fadd23 c-terminal domain in catalytic mechanisms |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989471/ https://www.ncbi.nlm.nih.gov/pubmed/36896429 http://dx.doi.org/10.3389/fmicb.2023.1090534 |
work_keys_str_mv | AT yanmengrong thekeyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT caolin thekeyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT zhaoli thekeyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT zhouweihong thekeyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT liuxiang thekeyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT zhangwei thekeyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT raozihe thekeyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT yanmengrong keyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT caolin keyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT zhaoli keyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT zhouweihong keyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT liuxiang keyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT zhangwei keyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms AT raozihe keyrolesofmycobacteriumtuberculosisfadd23cterminaldomainincatalyticmechanisms |