Thermodynamics of semi-specific ligand recognition: the binding of dipeptides to the E.coli dipeptide binding protein DppA

Zainol, Mohamad K.M.; Linforth, Robert J.C.; Winzor, Donald J.; Scott, David J.

Abstract

This investigation of the temperature dependence of DppA interactions with a subset of three dipeptides (AA. AF and FA) by isothermal titration calorimetry has revealed the negative heat capacity (ΔCpo) that is a characteristic of hydrophobic interactions. The observation of enthalpy–entropy compensation is interpreted in terms of the increased structuring of water molecules trapped in a hydrophobic environment, the enthalpic energy gain from which is automatically countered by the entropy decrease associated with consequent loss of water structure flexibility. Specificity for dipeptides stems from appropriate spacing of designated DppA aspartate and arginine residues for electrostatic interaction with the terminal amino and carboxyl groups of a dipeptide, after which the binding pocket closes to become completely isolated from the aqueous environment. Any differences in chemical reactivity of the dipeptide sidechains are thereby modulated by their occurrence in a hydrophobic environment where changes in the structural state of entrapped water molecules give rise to the phenomenon of enthalpy–entropy compensation. The consequent minimization of differences in the value of ΔG0 for all DppA–dipeptide interactions thus provides thermodynamic insight into the biological role of DppA as a transporter of all dipeptides across the periplasmic membrane.

• Journal Article Type: Article
• Acceptance Date: Sep 18, 2021
• Online Publication Date: Oct 5, 2021
• Publication Date: 2021-12
• Deposit Date: Oct 1, 2021
• Publicly Available Date: Oct 5, 2021
• Journal: European Biophysics Journal
• Print ISSN: 0175-7571
• Electronic ISSN: 1432-1017
• Publisher: Springer Science and Business Media LLC
• Peer Reviewed: Peer Reviewed
• Volume: 50
• Issue: 8
• Pages: 1103-1110
• DOI: https://doi.org/10.1007/s00249-021-01572-y
• Keywords: General Medicine; Biophysics
• Public URL: https://nottingham-repository.worktribe.com/output/6349601
• Publisher URL: https://link.springer.com/article/10.1007%2Fs00249-021-01572-y
• Additional Information: Received: 15 June 2021; Revised: 23 August 2021; Accepted: 18 September 2021; First Online: 5 October 2021