hrvatski jezikClear Cookie - decide language by browser settings

Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study

Tomin, Marko; Tomić, Sanja (2017) Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study. Molecular BioSystems, 13 . pp. 2407-2417. ISSN 1742-206X

PDF - Accepted Version - article
Download (1MB) | Preview


Dipeptidyl peptidase III (DPP III) from the human gut symbiont Bacteroides thetaiotaomicron (Bt) is the first identified prokaryotic DPP III orthologue. It has low sequence similarity to the thoroughly studied human DPP III, and differently from eukaryotic orthologues it has a cysteine (Cys450) residue in the zinc-binding motif HEXXGH (HECLGH). The recently determined crystal structure of BtDPP III showed that its 3D structure, similar to the structure of the human DPP III, consists of two domains with a wide cleft in between. Although such a striking similarity of the 3D structures of orthologues with low sequence similarity is not surprising, it is no guarantee for similarity of their dynamic properties and the catalytic performance. Here, we report the results of the molecular modelling study of BtDPP III, wild type and its C450S mutant, as well as their complexes with characteristic DPP III substrates Arg–Arg–2-naphthylamide (RRNA) and Lys–Ala–2-naphtylamide (KANA). During several hundred nanoseconds of all-atom MD simulations of the wild type protein, the long range conformational changes, which can be described as protein ‘closing’, have been traced. We have determined a similar conformational change for the human orthologue as well. However, the amplitude of the change is lower for BtDPP III than for the human DPP III. The MD simulations have been performed using ff03, ff12SB and ff14SB force fields wherein the results of the last two better fit to the experimental results. The hydrogen bond analysis indicates reasons for higher substrate specificity of BtDPP III towards RRNA than KANA as well as for the decrease of the RRNA hydrolysis rate induced by the Cys450 to Ser mutation. The obtained results are in line with the experimental data.

Item Type: Article
Additional Information: The work was supported by Croatian Science Foundation under the project "7235 Flexibility, activity and structure correlations in the dipeptidyl peptidase III family''. Some of the calculations have been performed at the Croatian National Grid Infrastructure (CRO NGI, We are grateful to Dr Maja Abramic for her valuable suggestions and fruitful discussion.
Uncontrolled Keywords: dipeptidyl peptidase III ; molecular dynamics ; accelerated molecular dynamics ; docking
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Division of Organic Chemistry and Biochemistry
Project titleProject leaderProject codeProject type
Povezanost fleksibilnosti, aktivnosti i strukture u porodici dipeptidil-peptidaza III-FlAcSSanja TomićIP-2013-11-7235HRZZ
Depositing User: Marko Tomin
Date Deposited: 20 Nov 2018 09:18
DOI: 10.1039/c7mb00310b

Actions (login required)

View Item View Item


Downloads per month over past year

Increase Font
Decrease Font
Dyslexic Font