Naslov
Oxidase or peptidase? A putative DPP III from Armillariella tabescens

Autori
Tomin, Marko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Computational Chemistry Day Book of abstracts / - Zagreb : Prirodoslovno-matematički fakultet Sveučilišta u Zagrebu, 2018, 27-27

ISBN
978-953-6076-45-1

Skup
Computational Chemistry Day 2018

Mjesto i datum
Zagreb, Hrvatska, 12.05.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
aflatoxin oxidase ; dipeptidyl peptidase III ; DPP III ; molecular dynamics

Sažetak
An enzyme isolated from the fungus Armillariella tabescens has been reported to break down aflatoxin B1 (AFB1), a potent toxin and carcinogen commonly found in food and animal feed, and subsequently dubbed aflatoxin oxidase (AFO). However, AFO shares high sequence similarity with dipeptidyl peptidase III (DPP III) while its recently determined crystal structure reveals an active site resembling the one of DPP III. Further on, recent studies report no oxidase activity while the peptidase activity was reported using both natural and synthetic substrates. In order to elucidate the role of the putative A. tabescens DPP III, docking and long MD simulations of its complexes with Arg2-2-naphthylamide and AFB1 were performed and respective binding energies were calculated using the MM-PBSA approach. In case of the AFB1 complex, two possible binding modes were considered. Both conventional and steered molecular dynamics were employed in an attempt to observe long-range conformational motions and locate the non-catalytic, so-called "open", form of the enzyme, present in other DPP III orthologs. In addition to the crystallographically determined "closed" form, an open form of the enzyme was identified, which is consistent with previous findings within the DPP III family. Docking results suggest that AFB1 binding to the enzyme is unfavorable, supporting the findings of Karačić et al. The synthetic substrates, namely dipeptidyl-2-naphthylamides, bind antiparallel to the conserved 384GINL β-sheet which is in line with crystallographic data for human DPP III.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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