Thermodynamics of unfolding of the alpha-amylase inhibitor tendamistat. Correlations between accessible surface area and heat capacity.


Abstract

Unfolding of the small alpha-amylase inhibitor tendamistat (74 residues, 2 disulfide bridges) has been characterized thermodynamically by high sensitivity scanning microcalorimetry. To link the stability parameters with structural information we use heat capacity group parameters and water accessible surface areas to calculate the change in heat capacity on unfolding of tendamistat. Our results show that both the group parameter and surface area approaches provide a reasonable, though not perfect, basis for delta Cp calculations. When using the experimentally determined temperature-independent heat capacity increase of 2.89 kJ mol-1 K-1 tendamistat exhibits convergence of thermodynamic parameters at about 140 degrees C, in agreement with recent predictions of the temperature at which the hydrophobic hydration is supposed to disappear. Despite the apparent support of this new view of the hydrophobic effect, there are inconsistencies in the interpretation of the thermodynamic parameters and these are addressed in the Discussion. The specific stability of tendamistat is similar to that of modified bovine pancreatic trypsin inhibitor, with only two of the native three disulfide bridges intact. This observation confirms our previous conclusion that disulfide bridges affect significantly the enthalpy and entropy of unfolding. The recent study by Doig & Williams provides additional convincing support for this conclusion. The predictive scheme proposed by these authors permits a fair estimate of the Gibbs free energy and enthalpy changes of these two proteins. Study holds ProTherm entries: 2854, 2855, 2856 Extra Details: tendamistat; unfolding; thermodynamics; heat capacity;,accessible surface area

Submission Details

ID: sif4VmU83

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:20 p.m.

Version: 1

Publication Details
Renner M;Hinz HJ;Scharf M;Engels JW,J. Mol. Biol. (1992) Thermodynamics of unfolding of the alpha-amylase inhibitor tendamistat. Correlations between accessible surface area and heat capacity. PMID:1542117
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
4AIT 1991-04-15 RESTRAINED ENERGY REFINEMENT WITH TWO DIFFERENT ALGORITHMS AND FORCE FIELDS OF THE STRUCTURE OF THE ALPHA-AMYLASE INHIBITOR TENDAMISTAT DETERMINED BY NMR IN SOLUTION
3AIT 1991-04-15 RESTRAINED ENERGY REFINEMENT WITH TWO DIFFERENT ALGORITHMS AND FORCE FIELDS OF THE STRUCTURE OF THE ALPHA-AMYLASE INHIBITOR TENDAMISTAT DETERMINED BY NMR IN SOLUTION
2AIT 1990-04-15 DETERMINATION OF THE COMPLETE THREE-DIMENSIONAL STRUCTURE OF THE ALPHA-AMYLASE INHIBITOR TENDAMISTAT IN AQUEOUS SOLUTION BY NUCLEAR MAGNETIC RESONANCE AND DISTANCE GEOMETRY
1OK0 2004-01-15 0.93 Crystal Structure of Tendamistat
1HOE 1989-04-19 2.0 CRYSTAL STRUCTURE DETERMINATION, REFINEMENT AND THE MOLECULAR MODEL OF THE ALPHA-AMYLASE INHIBITOR HOE-467A
1BVN 1998-09-23 2.5 PIG PANCREATIC ALPHA-AMYLASE IN COMPLEX WITH THE PROTEINACEOUS INHIBITOR TENDAMISTAT

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Alpha-amylase inhibitor HOE-467A P01092 IAA_STRTE