Pregled bibliografske jedinice broj: 1236243
Dipeptidyl peptidase iii inhibition tests by metal dications
Dipeptidyl peptidase iii inhibition tests by metal dications // Book of Abstracts of the Congress of the Croatian Society of Biochemistry and Molecular Biology HDBMB22: From Science to Knowledge / Dulić, Morana ; Sinčić, Nino ; Vrhovac Madunić, Ivana (ur.).
Zagreb: Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2022. str. 105-105 (poster, nije recenziran, sažetak, znanstveni)
CROSBI ID: 1236243 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Dipeptidyl peptidase iii inhibition tests by metal dications
Autori
Matić, Antonia ; Karačić, Zrinka ; Tomić, Antonija ; Brkić, Hrvoje ; Tomić Sanja
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
Book of Abstracts of the Congress of the Croatian Society of Biochemistry and Molecular Biology HDBMB22: From Science to Knowledge
/ Dulić, Morana ; Sinčić, Nino ; Vrhovac Madunić, Ivana - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2022, 105-105
Skup
International Congress of the Croatian Society of Biochemistry and Molecular Biology HDBMB22: From Science to Knowledge
Mjesto i datum
Brela, Hrvatska, 28.09.2022. - 01.10.2022
Vrsta sudjelovanja
Poster
Vrsta recenzije
Nije recenziran
Ključne riječi
hDppIII ; matali Zn ; Mn ; Cu ; Co ; inhibicija
(hDppIII ; matal Zn ; Mn ; Cu ; Co ; inhibition)
Sažetak
It has long been known that the peptidase activity of human dipeptidyl peptidase III (hDPP III) is inhibited by excess zinc ions. The aim of my paper is to determine the effects of different concentrations of metal dication: Zn2+, Mn2+, Co2+ and Cu2+ on the activity of hDPP III and to identify the inhibitory binding site of the metal. The existence of an inhibitory binding site was hypothesized based on a decrease in hDPP III activity at higher zinc concentrations and the similarity of hDPP III active site with those of carboxypeptidase A and thermolysin in whose crystallographic structures binding of another metal ion was observed in the immediate vicinity of the catalytically active ion. Inhibition of hDPP III by metal dications (Zn2+, Mn2+, Co2+ and Cu2+) is being investigated using various experimental and computational methods. For the purposes of experimental research, we prepare holoenzymes by incubating hDPP III with different concentrations of Zn2+, Mn2+, Co2+ and Cu2+ ions. In the samples thus prepared, metal-protein stoichometry is determined by high-resolution mass spectrometry with inductively coupled plasma (HRICP-MS) and microcalorimetric methods (isothermal titration calorimetry, ITC). Using the stopped-flow method, we monitor the decrease in hDPP III enzymatic activity caused by excess metal dications. Finally, using molecular dynamics combined with free binding energy calculus and quantum mechanical - molecular mechanical calculations we identified the zinc binding site and its effect on hDPP III structure and dynamics. Also, following the path of zinc ion exchange, we concluded that, as in the case of anthrax lethal factor, it is the so- called associative mode of modification described by relations: . enzyme ̶metal A + metal B ↔enzyme ̶metal A ̶metal B i. enzyme ̶metal A ̶metal B ↔enzyme ̶metal B +metal A . The results of this study allowed us to propose a mechanism by which the inhibitory zinc ion reduces enzyme activity.
Izvorni jezik
Engleski
Znanstvena područja
Kemija
POVEZANOST RADA
Projekti:
HRZZ-IP-2018-01-2936 - Biološka važnost dipeptidil peptidaze III i njezin utjecaj na zdravlje čovjeka (DPP3BioRe) (Tomić, Sanja, HRZZ - 2018-01) ( CroRIS)
Ustanove:
Institut "Ruđer Bošković", Zagreb
Profili:
Zrinka Karačić (autor)
Sanja Tomić (autor)
Hrvoje Brkić (autor)
Antonia Matić (autor)
Antonija Tomić (autor)