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Pregled bibliografske jedinice broj: 525128

Časopis

Autori: Špoljarić, Jasminka; Tomić, Antonija; Vukelić, Bojana; Salopek-Sondi, Branka; Agić, Dejan; Tomić, Sanja; Abramić, Marija
Naslov: Human Dipeptidyl Peptidase III : the Role of Asn406 in Ligand Binding and Hydrolysis
( Human Dipeptidyl Peptidase III : the Role of Asn406 in Ligand Binding and Hydrolysis )
Izvornik: Croatica chemica acta (0011-1643) 84 (2011), 2; 259-268
Vrsta rada: članak
Ključne riječi: dipeptidyl peptidase III; molecular dynamics; peptidase family M49; protein structure-function; site-directed mutagenesis
( 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.
Projekt / tema: 098-0982913-2829, 098-1191344-2860, 098-1191344-2938
Izvorni jezik: eng
Rad je indeksiran u
bazama podataka:
Current Contents Connect (CCC)
Scopus
SCI-EXP, SSCI i/ili A&HCI
Science Citation Index Expanded (SCI-EXP) (sastavni dio Web of Science Core Collectiona)
Kategorija: Znanstveni
Znanstvena područja:
Kemija,Biologija
URL Internet adrese: http://hrcak.srce.hr/index.php?show=clanak&id_clanak_jezik=107224
Broj citata:
Altmetric:
DOI: 10.5562/cca1808
URL cjelovitog teksta:
Google Scholar: Human Dipeptidyl Peptidase III : the Role of Asn406 in Ligand Binding and Hydrolysis
Upisao u CROSBI: atomic@irb.hr (atomic@irb.hr), 13. Ruj. 2011. u 10:19 sati



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