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Original scientific paper

https://doi.org/10.5562/cca3343

The Mechanism of Peptide Hydrolysis Catalysed by Dipeptidyl Peptidase III from Bacteroides thetaiotaomicron

Marko Tomin orcid id orcid.org/0000-0001-6894-6810 ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia
Antonija Tomić ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia
Borislav Kovačević ; Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia
Sanja Tomić orcid id orcid.org/0000-0002-0550-0878 ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia


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Abstract

Dipeptidyl peptidase III (DPP III) is a zinc-dependent peptidase that cleaves dipeptides off of N-termini of its substrates. Previous studies on human DPP III reveal a reaction mechanism similar to that of thermolysin. Since the active site is conserved within the DPP III family, it is not surprising that the mechanism determined for Bacteroides thetaiotaomicron DPP III (BtDPP III) closely resembles that of hDPP III. However, the hydrogen bond network within the model differs slightly from that in the human ortholog, which results in two proposed pathways. The calculated Gibbs activation energy of 90.1 kJ mol–1 is larger than the one calculated from kinetic data for the preferred substrate Arg2-2-naphthylamide at room temperature (69 kJ mol–1), suggesting the importance of treating the whole DPP III enzyme in the calculations.

This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords

dipeptidyl peptidase III; DPP III; peptide hydrolysis; reaction mechanism; Bacteroides thetaiotaomicron

Hrčak ID:

201073

URI

https://hrcak.srce.hr/201073

Publication date:

4.6.2018.

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