The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F21%3A00123501" target="_blank" >RIV/00216224:14310/21:00123501 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2021/CP/D1CP03718H" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2021/CP/D1CP03718H</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d1cp03718h" target="_blank" >10.1039/d1cp03718h</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physical Chemistry Chemical Physics

ISSN

1463-9076

e-ISSN

—

Svazek periodika

23

Číslo periodika v rámci svazku

41

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

23850-23860

Kód UT WoS článku

000707181700001

EID výsledku v databázi Scopus

2-s2.0-85118442322