title: Bovine α₁-acid glycoprotein, a thermostable version of its human counterpart: insights from Fourier transform infrared spectroscopy and in silico modelling.
abstract: α1-Acid glycoprotein (AGP) is a plasma protein and a member of the acute phase response. AGP is known to bind and carry several biologically active compounds, as well as to down-modulate the immune system activities. In this work, the structure of bovine AGP has been investigated by Fourier-Transform infrared spectroscopy. A model structure has been obtained on the basis of human AGP and refined by molecular dynamics. In spite of the similar structure, bovine AGP shows an unexpectedly higher (∼20 °C) thermostability than its human counterpart. Inspection of the model structure has pointed out the presence of 12 ionic bridges and 2 sulphur-aromatic interactions, whereas only 6 ionic bridges were detected in human AGP. The high number (9) of glutamic acid residues involved in the ionic interactions might explain the significantly decreased thermostability measured at pH 5.5 (Tm ∼ 71 °C) with respect to pH 7.4 (Tm ∼ 81 °C), whereas thermostability of human AGP was only slightly affected by lowering the pH. As in human AGP and several other lipocalins, a temperature-induced molten globule state has been observed in the denaturation pathway of bovine AGP.
authors: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.
authors: Maurizio
authors: M
authors: Baldassarre
authors: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.
authors: Roberta
authors: R
authors: Galeazzi
authors: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.
authors: Beatrice
authors: B
authors: Maggiore
authors: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.
authors: Fabio
authors: F
authors: Tanfani
authors: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy. Electronic address: a.a.scire@univpm.it.
authors: Andrea
authors: A
authors: Scirè
mesh_terms: D000818:Animals; D002417:Cattle; D003198:Computer Simulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D054834:Lipocalins / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009961:Orosomucoid / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D054834:Lipocalins; D009961:Orosomucoid
keywords: FT-IR spectroscopy; Lipocalins; Molecular dynamics; Molten globule-like state; Thermostability; α(1)-acid glycoprotein