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Human Dipeptidyl Peptidase III : the Role of Asn406 in Ligand Binding and Hydrolysis


Špoljarić, Jasminka; Tomić, Antonija; Vukelić, Bojana; Salopek-Sondi, Branka; Agić, Dejan; Tomić, Sanja; Abramić, Marija
Human Dipeptidyl Peptidase III : the Role of Asn406 in Ligand Binding and Hydrolysis // Croatica chemica acta, 84 (2011), 2; 259-268 doi:10.5562/cca1808 (međunarodna recenzija, članak, znanstveni)


Naslov
Human Dipeptidyl Peptidase III : the Role of Asn406 in Ligand Binding and Hydrolysis

Autori
Špoljarić, Jasminka ; Tomić, Antonija ; Vukelić, Bojana ; Salopek-Sondi, Branka ; Agić, Dejan ; Tomić, Sanja ; Abramić, Marija

Izvornik
Croatica chemica acta (0011-1643) 84 (2011), 2; 259-268

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Dipeptidyl peptidase III; molecular dynamics; peptidase family M49; protein structure-function; site-directed mutagenesis

Sažetak
Human dipeptidyl peptidase III (DPP III) is a member of the zinc-metallopeptidase family M49 with a role in intracellular protein catabolism. Ligand-free crystal structure of yeast and human orthologues provided insight into the enzyme's active center and enabled some assumptions about the enzyme-substrate interactions. The molecular modeling performed for human and yeast DPP III indicated involvement of Asn406 and Asn415, respectively in ligand binding. To investigate further the role of this asparagine residue, conserved in all eukaryotic M49 peptidases, a site-directed mutagenesis of human DPP III was carried out. Replacement of Asn406 with Gln, but not with Ser, resulted in a large decrease in the enzyme's binding affinity for competitive peptide inhibitor and in catalytic efficiency. Molecular dynamics simulations performed for enzyme-substrate complexes, revealed changed coordination of the active-site zinc ion and the orientation of the catalytically important His568, in N406Q, but not in the N406S complexes.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija



POVEZANOST RADA


Projekt / tema
098-0982913-2829 - Molekularna regulacija biljnog razvitka (Branka Salopek-Sondi, )
098-1191344-2860 - Proučavanje biomakromolekula računalnim metodama i razvoj novih algoritama (Sanja Tomić, )
098-1191344-2938 - Molekularna enzimologija i proteinske interakcije hidrolaza (Marija Abramić, )

Ustanove
Institut "Ruđer Bošković", Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus


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