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Pregled bibliografske jedinice broj: 956077

Aprotinin interacts with substrate-binding site of human dipeptidyl peptidase III

Agić, Dejan; Brkić, Hrvoje; Kazazić, Saša; Tomić, Antonija; Abramić, Marija
Aprotinin interacts with substrate-binding site of human dipeptidyl peptidase III // Journal of Biomolecular Structure and Dynamics, 37 (2019), 14; 3596-3606 doi:10.1080/07391102.2018.1521343 (međunarodna recenzija, članak, znanstveni)

Aprotinin interacts with substrate-binding site of human dipeptidyl peptidase III

Agić, Dejan ; Brkić, Hrvoje ; Kazazić, Saša ; Tomić, Antonija ; Abramić, Marija

Journal of Biomolecular Structure and Dynamics (0739-1102) 37 (2019), 14; 3596-3606

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

Ključne riječi
Aprotinin ; BPTI ; dipeptidyl peptidase III ; metallopeptidase ; MD simulation

Human dipeptidyl peptidase III (hDPP III) is a zinc-exopeptidase of the family M49 involved in final steps of intracellular protein degradation and in cytoprotective pathway Keap1-Nrf2. Biochemical and structural properties of this enzyme have been extensively investigated, but the knowledge on its contacts with other proteins is scarce. Previously, polypeptide aprotinin was shown to be a competitive inhibitor of hDPP III hydrolytic activity. In the present study, aprotinin was first investigated as a potential substrate of hDPP III, but no degradation products were demonstrated by MALDI-TOF mass spectrometry. Subsequently, molecular details of the protein-protein interaction between aprotinin and hDPP III were studied by molecular modeling. Docking and long molecular dynamics (MD) simulations have shown that aprotinin interacts by its canonical binding epitope with the substrate binding cleft of hDPP III. Thereby, free N-terminus of aprotinin is distant from the active-site zinc. Enzyme-inhibitor complex is stabilized by intermolecular hydrogen bonding network, electrostatic and hydrophobic interactions which mostly involve constituent amino acid residues of the hDPP III substrate binding subsites S1, S1', S2, S2' and S3'. This is the first study that gives insight into aprotinin binding to an metallopeptidase

Izvorni jezik

Znanstvena područja
Fizika, Kemija, Biologija


Fakultet agrobiotehničkih znanosti Osijek,
Institut "Ruđer Bošković", Zagreb,
Medicinski fakultet, Osijek,
Fakultet za dentalnu medicinu i zdravstvo, Osijek

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