TY  - JOUR
A1  - Niesteruk, Anna
A1  - Sreeramulu, Sridhar
A1  - Jonker, Hendrik R. A.
A1  - Richter, Christian
A1  - Schwalbe, Harald
T1  - Oxidation of the Mycobacterium tuberculosis key virulence factor protein tyrosine phosphatase A (MptpA) reduces its phosphatase activity
T2  - FEBS Letters
N2  - The Mycobacterium tuberculosis tyrosine-specific phosphatase MptpA and its cognate kinase PtkA are prospective targets for anti-tuberculosis drugs as they interact with the host defense response within the macrophages. Although both are structurally well-characterized, the functional mechanism regulating their activity remains poorly understood. Here, we investigate the effect of post-translational oxidation in regulating the function of MptpA. Treatment of MptpA with H2O2/NaHCO3, mimicking cellular oxidative stress conditions, leads to oxidation of the catalytic cysteine (C11) and to a conformational rearrangement of the phosphorylation loop (D-loop) by repositioning the conserved tyrosine 128 (Y128) and generating a temporarily inactive preclosed state of the phosphatase. Thus, the catalytic cysteine in the P-loop acts as a redox switch and regulates the phosphatase activity of MptpA.
KW  - cysteine-redox regulation
KW  - Mycobacterium tuberculosis
KW  - nuclear magnetic resonance spectroscopy
KW  - protein oxidation
KW  - protein tyrosine phosphatase
KW  - reactive oxygen species
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/70608
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-706087
SN  - 1873-3468
N1  - This work was supported in part by the DKTK (German Consortium for Translational Cancer Research), FOR2509 (German Research Foundation, DFG), and iNEXT-Discovery, project number 871037, funded by the Horizon 2020 program of the European Commission. The work at BMRZ was supported by the State of Hesse.
VL  - 596
IS  - 12
SP  - 1503
EP  - 1515
PB  - Wiley
CY  - Chichester
ER  -