Computational study of dipeptidyl peptidase III from thermophile Caldithrix abyssi (CROSBI ID 649412)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Tomin, Marko ; Tomić, Sanja
engleski
Computational study of dipeptidyl peptidase III from thermophile Caldithrix abyssi
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.
termophile ; dynamics ; DPP III
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Podaci o prilogu
16-16.
2017.
objavljeno
Podaci o matičnoj publikaciji
Vančik, Hrvoj ; Cioslowski, Jerzy
Podaci o skupu
Math/Chem/Comp 2017, MC2-29 : The 29th International Course and Conference on the Interfaces among Mathematics, Chemistry and Computer Sciences
poster
19.06.2017-24.06.2017
Dubrovnik, Hrvatska