The catalytic reaction mechanism of tyrosylprotein
sulfotransferase-1

J 2021

The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1

ŠMAK, Pavel, Igor TVAROŠKA a Jaroslav KOČA

Základní údaje

Originální název

The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1

Autoři

ŠMAK, Pavel (203 Česká republika, domácí), Igor TVAROŠKA (703 Slovensko, garant, domácí) a Jaroslav KOČA (203 Česká republika, domácí)

Vydání

Physical Chemistry Chemical Physics, Royal Society of Chemistry, 2021, 1463-9076

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10403 Physical chemistry

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.945

Kód RIV

RIV/00216224:14310/21:00123501

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1039/d1cp03718h

UT WoS

000707181700001

Klíčová slova anglicky

Density functional theory; Molecular dynamics; Protein; Adhesion; Prification; TransitionTyrosine sulfation; Selectin; Envelope glycoprotein; Cancer cells

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 1. 2022 15:33, Mgr. Marie Šípková, DiS.

Anotace

V originále

Tyrosine sulfation alters the biological activity of many proteins involved in different physiological and pathophysiological conditions, such as non-specific immune reaction, response to inflammation and ischemia, targeting of leukocytes and stem cells, or the formation of cancer metastases. Tyrosine sulfation is catalyzed by the enzymes tyrosylprotein sulfotransferases (TPST). In this study, we used QM/MM Car-Parrinello metadynamics simulations together with QM/MM potential energy calculations to investigate the catalytic mechanism of isoform TPST-1. The structural changes along the reaction coordinate are analyzed and discussed. Furthermore, both the methods supported the S(N)2 type of catalytic mechanism. The reaction barrier obtained from CPMD metadynamics was 12.8 kcal mol(-1), and the potential energy scan led to reaction barriers of 11.6 kcal mol(-1) and 13.7 kcal mol(-1) with the B3LYP and OPBE functional, respectively. The comparison of the two methods (metadynamics and potential energy scan) may be helpful for future mechanistic studies. The insight into the reaction mechanism of TPST-1 might help with the rational design of transition-state TPST inhibitors.

Návaznosti

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

ŠMAK, Pavel, Igor TVAROŠKA a Jaroslav KOČA. The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1. Physical Chemistry Chemical Physics. Royal Society of Chemistry, 2021, roč. 23, č. 41, s. 23850-23860. ISSN 1463-9076. Dostupné z: https://dx.doi.org/10.1039/d1cp03718h.

@article{1816743,
   author = {Šmak, Pavel and Tvaroška, Igor and Koča, Jaroslav},
   article_number = {41},
   doi = {http://dx.doi.org/10.1039/d1cp03718h},
   keywords = {Density functional theory; Molecular dynamics; Protein; Adhesion; Prification; TransitionTyrosine sulfation; Selectin; Envelope glycoprotein; Cancer cells},
   language = {eng},
   issn = {1463-9076},
   journal = {Physical Chemistry Chemical Physics},
   title = {The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1},
   url = {https://pubs.rsc.org/en/content/articlelanding/2021/CP/D1CP03718H},
   volume = {23},
   year = {2021}
}

TY  - JOUR
ID  - 1816743
AU  - Šmak, Pavel - Tvaroška, Igor - Koča, Jaroslav
PY  - 2021
TI  - The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1
JF  - Physical Chemistry Chemical Physics
VL  - 23
IS  - 41
SP  - 23850-23860
EP  - 23850-23860
PB  - Royal Society of Chemistry
SN  - 14639076
KW  - Density functional theory
KW  - Molecular dynamics
KW  - Protein
KW  - Adhesion
KW  - Prification
KW  - TransitionTyrosine sulfation
KW  - Selectin
KW  - Envelope glycoprotein
KW  - Cancer cells
UR  - https://pubs.rsc.org/en/content/articlelanding/2021/CP/D1CP03718H
N2  - Tyrosine sulfation alters the biological activity of many proteins involved in different physiological and pathophysiological conditions, such as non-specific immune reaction, response to inflammation and ischemia, targeting of leukocytes and stem cells, or the formation of cancer metastases. Tyrosine sulfation is catalyzed by the enzymes tyrosylprotein sulfotransferases (TPST). In this study, we used QM/MM Car-Parrinello metadynamics simulations together with QM/MM potential energy calculations to investigate the catalytic mechanism of isoform TPST-1. The structural changes along the reaction coordinate are analyzed and discussed. Furthermore, both the methods supported the S(N)2 type of catalytic mechanism. The reaction barrier obtained from CPMD metadynamics was 12.8 kcal mol(-1), and the potential energy scan led to reaction barriers of 11.6 kcal mol(-1) and 13.7 kcal mol(-1) with the B3LYP and OPBE functional, respectively. The comparison of the two methods (metadynamics and potential energy scan) may be helpful for future mechanistic studies. The insight into the reaction mechanism of TPST-1 might help with the rational design of transition-state TPST inhibitors.
ER  -

ŠMAK, Pavel, Igor TVAROŠKA a Jaroslav KOČA. The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1. \textit{Physical Chemistry Chemical Physics}. Royal Society of Chemistry, 2021, roč.~23, č.~41, s.~23850-23860. ISSN~1463-9076. Dostupné z: https://dx.doi.org/10.1039/d1cp03718h.

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