Pregled bibliografske jedinice broj: 1212363
Computational study of the human DPP III catalyzed peptide hydrolysis - difference between „good“ and „slow“ substrate
Computational study of the human DPP III catalyzed peptide hydrolysis - difference between „good“ and „slow“ substrate // Math/Chem/Comp 2022 and 33rd MC2 Conference : Book of Abstracts / Vančik, Hrvoj ; Cioslowski, Jerzy ; Namjesnik, Danijel (ur.).
Zagreb: Hrvatsko kemijsko društvo, 2022. str. 24-24 (predavanje, nije recenziran, sažetak, znanstveni)
CROSBI ID: 1212363 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Computational study of the human DPP III catalyzed
peptide hydrolysis - difference between „good“ and
„slow“ substrate
Autori
Tomić, Antonija ; Tomić, Sanja
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
Math/Chem/Comp 2022 and 33rd MC2 Conference : Book of Abstracts
/ Vančik, Hrvoj ; Cioslowski, Jerzy ; Namjesnik, Danijel - Zagreb : Hrvatsko kemijsko društvo, 2022, 24-24
ISBN
978-953-8334-03-0
Skup
33rd MC2 Conference (Math/Chem/Comp 2022)
Mjesto i datum
Dubrovnik, Hrvatska, 06.06.2022. - 10.06.2022
Vrsta sudjelovanja
Predavanje
Vrsta recenzije
Nije recenziran
Ključne riječi
dipeptidyl peptides III ; tynorphin ; Leu-enkephalin ; peptide hydrolysis ; QMMM calculations
Sažetak
Dipeptidyl peptides III (DPP III) is a two-domain zinc containing enzyme that cleaves dipeptide from the unsubstituted N-terminus of its substrates. Substrates are peptides of different sequences and sizes, with tetrapeptides to octapeptides being the best one [1]. There have been several attempts to explain DPP III broad substrate promiscuity and to rationalize why some of the peptides are effectively cleaved by DPP III (“good” substrates) while the others are not (“slow” substrates) showing high inhibition potency. Combining quantum molecular mechanics calculations, molecular dynamic simulations and the free energy calculations (MM/P(G)BSA) we have offered possible explanations. The enzymatic cycle of human DPP III i.e. the substrate binding to the active site of the enzyme, the peptide bond hydrolysis and release of the products were described for enzyme in complex with tynorphin, “slow” substrate, and Leu- enkephalin. The study showed that the reason for much slower processing of tynorphin than Leu- enkephalin is not the difference in the reaction mechanism, but the significantly higher stabilization of the products of tynorphin hydrolysis, which impede the regeneration of the enzyme. That is, the energies required for nucleophilic attack of the catalytic water molecule and inversion at the nitrogen atom of the cleavable peptide bond, which corresponds to the rate-determining step of peptide hydrolysis by DPP III, are similar for both ligands.
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