Reorganization in apo- and holo-beta-lactoglobulin upon protonation of Glu89: molecular dynamics and pKa calculations
Articolo
Data di Pubblicazione:
2004
Citazione:
Reorganization in apo- and holo-beta-lactoglobulin upon protonation of Glu89: molecular dynamics and pKa calculations / I. Eberini, A. M. Baptista, E. Gianazza, F. Fraternali, T. Beringhelli. - In: PROTEINS. - ISSN 0887-3585. - 54:4(2004), pp. 744-758. [10.1002/prot.10643]
Abstract:
Molecular dynamics (MD) simulations starting from crystallographic data allowed us to directly account for the effects of the protonation state of Glu89 on the conformational stability of apo- and holo-beta-lactoglobulin (BLG). In apo-BLG simulations starting from the protonated crystal structure, we observe a long-lived H-bond interaction between the protonated Glu89 and Ser116. This interaction, sequestering the proton from the aqueous medium, explains a pK(half) value evaluated at pH 7.3 by continuum electrostatics/Monte Carlo computation on MD data, using linear response approximation. A very large root-mean-square deviation (RMSD; 5.11 A) is observed for the EF loop between protonated and unprotonated apo-BLG. This results from a quite different orientation of the EF loop that acts either as a closed or as an open lid above the protein calyx. Proton exchange by Glu89 in apo- but not in holo-BLG is associated with a reorganization energy of 4.7 kcal/mol. A 3-ns MD simulation starting from the crystal structure of protonated apo-BLG, but considering the Glu89 as unprotonated, shows the progressive opening of the lid giving rise to the Tanford transition. In both holo-BLG forms, the lid is most probably held in place by hydrophobic interactions of amino acid side-chains of the EF loop with the palmitate hydrocarbon tail.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Electrostatics; Hydrogen bond; Linear response approximation; Palmitate; Salt bridge; Secondary structure; Tanford transition
Elenco autori:
I. Eberini, A.M. Baptista, E. Gianazza, F. Fraternali, T. Beringhelli
Link alla scheda completa: