Para-aminosalicylic acid is a prodrug targeting dihydrofolate reductase in mycobacterium tuberculosis

Jun Zheng; Eric J. Rubin; Pablo Bifani; Vanessa Mathys; Vivian Lim; Melvin Au; Jichan Jang; Jiyoun Nam; Thomas Dick; John R. Walker; Kevin Pethe; Luis R. Camacho

doi:10.1074/jbc.M113.475798

Para-aminosalicylic acid is a prodrug targeting dihydrofolate reductase in mycobacterium tuberculosis

Jun Zheng
, Eric J. Rubin
, Pablo Bifani
, Vanessa Mathys
, Vivian Lim
, Melvin Au
, Jichan Jang
, Jiyoun Nam
, Thomas Dick
, John R. Walker
, Kevin Pethe
, Luis R. Camacho

Center for Discovery and Innovation

Hackensack Meridian School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Background: PAS is an antimycobacterial whose mechanism(s) of action remains elusive. Results: PAS is incorporated into the folate pathway by DHPS-DHFS, generating an anti-metabolite. DHFS and RibD are associated with PAS resistance. Conclusion: Hydroxyl dihydrofolate inhibits DHFR. folC and ribD are drug target genes for identification of clinical PAS resistance. Significance: Metabolite analog incorporation into essential biosynthetic pathways is promising for developing antibacterials.

Original language	English
Pages (from-to)	23447-23456
Number of pages	10
Journal	Journal of Biological Chemistry
Volume	288
Issue number	32
DOIs	https://doi.org/10.1074/jbc.M113.475798
State	Published - Aug 9 2013

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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10.1074/jbc.M113.475798

Cite this

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title = "Para-aminosalicylic acid is a prodrug targeting dihydrofolate reductase in mycobacterium tuberculosis",

abstract = "Background: PAS is an antimycobacterial whose mechanism(s) of action remains elusive. Results: PAS is incorporated into the folate pathway by DHPS-DHFS, generating an anti-metabolite. DHFS and RibD are associated with PAS resistance. Conclusion: Hydroxyl dihydrofolate inhibits DHFR. folC and ribD are drug target genes for identification of clinical PAS resistance. Significance: Metabolite analog incorporation into essential biosynthetic pathways is promising for developing antibacterials.",

author = "Jun Zheng and Rubin, \{Eric J.\} and Pablo Bifani and Vanessa Mathys and Vivian Lim and Melvin Au and Jichan Jang and Jiyoun Nam and Thomas Dick and Walker, \{John R.\} and Kevin Pethe and Camacho, \{Luis R.\}",

year = "2013",

month = aug,

day = "9",

doi = "10.1074/jbc.M113.475798",

language = "English",

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TY - JOUR

T1 - Para-aminosalicylic acid is a prodrug targeting dihydrofolate reductase in mycobacterium tuberculosis

AU - Zheng, Jun

AU - Rubin, Eric J.

AU - Bifani, Pablo

AU - Mathys, Vanessa

AU - Lim, Vivian

AU - Au, Melvin

AU - Jang, Jichan

AU - Nam, Jiyoun

AU - Dick, Thomas

AU - Walker, John R.

AU - Pethe, Kevin

AU - Camacho, Luis R.

PY - 2013/8/9

Y1 - 2013/8/9

N2 - Background: PAS is an antimycobacterial whose mechanism(s) of action remains elusive. Results: PAS is incorporated into the folate pathway by DHPS-DHFS, generating an anti-metabolite. DHFS and RibD are associated with PAS resistance. Conclusion: Hydroxyl dihydrofolate inhibits DHFR. folC and ribD are drug target genes for identification of clinical PAS resistance. Significance: Metabolite analog incorporation into essential biosynthetic pathways is promising for developing antibacterials.

AB - Background: PAS is an antimycobacterial whose mechanism(s) of action remains elusive. Results: PAS is incorporated into the folate pathway by DHPS-DHFS, generating an anti-metabolite. DHFS and RibD are associated with PAS resistance. Conclusion: Hydroxyl dihydrofolate inhibits DHFR. folC and ribD are drug target genes for identification of clinical PAS resistance. Significance: Metabolite analog incorporation into essential biosynthetic pathways is promising for developing antibacterials.

UR - https://www.scopus.com/pages/publications/84881409003

U2 - 10.1074/jbc.M113.475798

DO - 10.1074/jbc.M113.475798

M3 - Article

C2 - 23779105

SN - 0021-9258

VL - 288

SP - 23447

EP - 23456

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 32

ER -

Para-aminosalicylic acid is a prodrug targeting dihydrofolate reductase in mycobacterium tuberculosis

Abstract

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