| JANOŠ, Pavel, Igor TVAROŠKA, Christoph DELLAGO a Jaroslav KOČA. Catalytic Mechanism of Processive GlfT2: Transition Path Sampling Investigation of Substrate Translocation. ACS Omega. Washington, D.C.: American Chemical Society, 2020, roč. 5, č. 34, s. 21374-21384. ISSN 2470-1343. Dostupné z: https://dx.doi.org/10.1021/acsomega.0c01434. |
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@article{1732013,
author = {Janoš, Pavel and Tvaroška, Igor and Dellago, Christoph and Koča, Jaroslav},
article_location = {Washington, D.C.},
article_number = {34},
doi = {http://dx.doi.org/10.1021/acsomega.0c01434},
keywords = {Chemical structure; Hydroxyls; Reaction mechanisms; Transition states; Computational chemistry},
language = {eng},
issn = {2470-1343},
journal = {ACS Omega},
title = {Catalytic Mechanism of Processive GlfT2: Transition Path Sampling Investigation of Substrate Translocation},
url = {https://doi.org/10.1021/acsomega.0c01434},
volume = {5},
year = {2020}
}
TY - JOUR
ID - 1732013
AU - Janoš, Pavel - Tvaroška, Igor - Dellago, Christoph - Koča, Jaroslav
PY - 2020
TI - Catalytic Mechanism of Processive GlfT2: Transition Path Sampling Investigation of Substrate Translocation
JF - ACS Omega
VL - 5
IS - 34
SP - 21374-21384
EP - 21374-21384
PB - American Chemical Society
SN - 24701343
KW - Chemical structure
KW - Hydroxyls
KW - Reaction mechanisms
KW - Transition states
KW - Computational chemistry
UR - https://doi.org/10.1021/acsomega.0c01434
L2 - https://doi.org/10.1021/acsomega.0c01434
N2 - We applied the transition path sampling (TPS) method to study the translocation step of the catalytic mechanism of galactofuranosyl transferase 2 (GlfT2). Using TPS in the field of enzymatic reactions is still relatively rare, and we show its effectiveness on this enzymatic system. We decipher an unknown mechanism of the translocation step and, thus, provide a complete understanding of the catalytic mechanism of GlfT2 at the atomistic level. The GlfT2 enzyme is involved in the formation of the mycobacterial cell wall and transfers galactofuranose (Galf) from UDP-Galf onto a growing acceptor Galf chain. The biosynthesis of the galactan chain is accomplished in a processive manner, with the growing acceptor substrate remaining bound to GlfT2. The glycosidic bond formed by GlfT2 between the two Gall residues alternates between beta-(1-6) and beta-(1-5) linkages. The translocation of the growing galactan between individual additions of Galf residues is crucial for the function of GlfT2. Analysis of unbiased trajectory ensembles revealed that the translocation proceeds differently depending on the glycosidic linkage between the last two Galf residues. We also showed that the protonation state of the catalytic residue Asp372 significantly influences the translocation. Approximate transition state structures and potential energy reaction barriers of the translocation process were determined. The calculated potential reaction barriers in the range of 6-14 kcal/mol show that the translocation process is not the rate-limiting step in galactan biosynthesis.
ER -
JANOŠ, Pavel, Igor TVAROŠKA, Christoph DELLAGO a Jaroslav KOČA. Catalytic Mechanism of Processive GlfT2: Transition Path Sampling Investigation of Substrate Translocation. \textit{ACS Omega}. Washington, D.C.: American Chemical Society, 2020, roč.~5, č.~34, s.~21374-21384. ISSN~2470-1343. Dostupné z: https://dx.doi.org/10.1021/acsomega.0c01434.
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