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Issue 24, 2018, Issue in Progress
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Conservation of the conformational dynamics and ligand binding within M49 enzyme family

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Abstract

The hydrogen deuterium exchange (HDX) mass spectrometry combined with molecular dynamics (MD) simulations was employed to investigate conformational dynamics and ligand binding within the M49 family (dipeptidyl peptidase III family). Six dipeptidyl peptidase III (DPP III) orthologues, human, yeast, three bacterial and one plant (moss) were studied. According to the results, all orthologues seem to be quite compact wherein DPP III from the thermophile Caldithrix abyssi seems to be the most compact. The protected regions are located within the two domains core and the overall flexibility profile consistent with semi-closed conformation as the dominant protein form in solution. Besides conservation of conformational dynamics within the M49 family, we also investigated the ligand, pentapeptide tynorphin, binding. By comparing HDX data obtained for unliganded protein with those obtained for its complex with tynorphin it was found that the ligand binding mode is conserved within the family. Tynorphin binds within inter-domain cleft, close to the lower domain β-core and induces its stabilization in all orthologues. Docking combined with MD simulations revealed details of the protein flexibility as well as of the enzyme–ligand interactions.

Graphical abstract: Conservation of the conformational dynamics and ligand binding within M49 enzyme family

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Supplementary files

Article information


Submitted
05 Dec 2017
Accepted
28 Mar 2018
First published
10 Apr 2018

This article is Open Access

RSC Adv., 2018,8, 13310-13322
Article type
Paper

Conservation of the conformational dynamics and ligand binding within M49 enzyme family

S. Kazazić, Z. Karačić, I. Sabljić, D. Agić, M. Tomin, M. Abramić, M. Dadlez, A. Tomić and S. Tomić, RSC Adv., 2018, 8, 13310
DOI: 10.1039/C7RA13059G

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