Halothane, an inhalational anesthetic agent, increases folding stability of serum albumin.


Abstract

Inhalational anesthetic agents are known to alter protein function, but the nature of the interactions underlying these effects remains poorly understood. We have used differential scanning calorimetry to study the effects of the anesthetic agent halothane on the thermally induced unfolding transition of bovine serum albumin. We find that halothane (0.6-10 mM) stabilizes the folded state of this protein, increasing its transition midpoint temperature from 62 to 71 degrees C. Binding of halothane to the native state of serum albumin thus outweighs any non-specific interactions between the thermally unfolded state of serum albumin and halothane in this concentration range. Based on the average enthalpy change DeltaH for unfolding of 170 kcal/mol, the increase from 62 to 71 degrees C corresponds to an additional Gibbs energy of stabilization (DeltaDeltaG) due to halothane of more than 4 kcal/mol. Analysis of the dependence of DeltaDeltaG on halothane concentration shows that thermal unfolding of a bovine serum albumin molecule is linked to the dissociation of about one halothane molecule at lower halothane concentrations and about six at higher halothane concentrations. Serum albumin is the first protein that has been shown to be stabilized by an inhalational anesthetic. Study holds ProTherm entries: 11750 Extra Details: Scan rate is 1.5 C/min differential scanning calorimetry; volatile anesthetic action; protein folding;,anesthetic-protein interaction; protein stability; general anesthesia mechanism

Submission Details

ID: 63MgZwoX3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:43 p.m.

Version: 1

Publication Details
Tanner JW;Eckenhoff RG;Liebman PA,Biochim. Biophys. Acta (1999) Halothane, an inhalational anesthetic agent, increases folding stability of serum albumin. PMID:10082932
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
2L7U 2011-05-18 Structure of CEL-PEP-RAGE V domain complex
4LUH 2014-09-17 2.2 Complex of ovine serum albumin with 3,5-diiodosalicylic acid
4LUF 2014-09-17 2.3 Crystal Structure of Ovine Serum Albumin
4F5S 2012-10-03 2.47 Crystal Structure of Bovine Serum Albumin
5ORF 2017-11-15 2.54 Structure of ovine serum albumin in P1 space group
4OR0 2014-06-04 2.58 Crystal Structure of Bovine Serum Albumin in complex with naproxen
4JK4 2013-07-24 2.65 Crystal Structure of Bovine Serum Albumin in complex with 3,5-diiodosalicylic acid
3V03 2012-01-04 2.7 Crystal structure of Bovine Serum Albumin

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
92.4 Serum albumin P14639 ALBU_SHEEP
100.0 Serum albumin P02769 ALBU_BOVIN