Naslov
Computational study of dipeptidyl peptidase III from thermophile Caldithrix abyssi

Autori
Tomin, Marko ; Tomić, Sanja

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

Izvornik
Math/Chem/Comp 2017, 29th MC2 Conference : Book of Abstracts / Vančik, Hrvoj ; Cioslowski, Jerzy - , 2017, 16-16

Skup
Math/Chem/Comp 2017, MC2-29 : The 29th International Course and Conference on the Interfaces among Mathematics, Chemistry and Computer Sciences

Mjesto i datum
Dubrovnik, Hrvatska, 19.06.2017. - 24.06.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
termophile ; dynamics ; DPP III

Sažetak
Dipeptidyl peptidase III isolated from the thermophilic bacteria Caldithrix abyssi (CaDPP III) is a two-domain zinc exopeptidase, a member of the M49 family according to the MEROPS database. Like the other DPPs III it cleaves dipeptides from the N-terminus of its substrates but differently from human, yeast and Bacteroides thetaiotaomicron (mesophile) ortholog, it has the pentapeptide, HEISH, instead of the hexapeptide motif HEXXGH in the active site. The aim of our study was to investigate structure and dynamics of CaDPP III and to find possible differences with already characterised DPPs III from mesophiles, especially DPP III from the mesophilic bacteria B. thetaiotaomicron, which might rationalize its higher stability and its higher temperature optimum determined experimentally. Further on in order to understand the structural and catalytic significance of the HEISH motif unique to C. abyssi, we also performed long MD simulations of the mutant with the HEISGH motive, as well as its complex with RRNA. The enzyme stability and the possible conformational changes were investigated using 200 ns long classical and accelerated MD simulations. We have identified distinct "open" and "closed" conformations in line with those previously reported for human DPP III and BtDPP III. During the simulations the zinc ion was mostly hexacoordinated with amino acid residues (His379, His383 and Glu412) and two to three water molecules. The simulations of CaDPP III complexes with synthetic substrates Arg2-2-naphtylamide (RRNA) and Gly-Arg-2-naphtylamide (GRNA) revealed their binding modes and helped us to rationalize the experimental data on their CaDPP III catalysed hydrolysis.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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