Contribution of the hydrophobic effect to the stability of human lysozyme: calorimetric studies and X-ray structural analyses of the nine valine to alanine mutants.


Abstract

To clarify the contribution of the hydrophobic effect to the conformational stability of human lysozyme, a series of Val to Ala mutants were constructed. The thermodynamic parameters for the denaturation of these nine mutant proteins were determined using differential scanning calorimetry (DSC), and the crystal structures were solved at high resolution. The denaturation Gibbs energy (delta delta G) and enthalpy (delta delta H) values of the mutant proteins ranged from +2.2 to- 6.3 kJ/mol and from +7 to -17 kJ/mol, respectively. The structural analyses showed that the mutation site and/or the residues around it in some proteins shifted toward the created cavity, and the substitutions affected not only the mutations site but also other parts far from the site, although the structural changes were not as great. Correlation between the changes in the thermodynamic parameters and the structural features of mutant proteins was examined, including the five Ile to Val mutant human lysozymes [Takano et al. (1995) J. Mol. Biol. 254, 62-76]. There was no simple general correlation between delta delta G and the changes in hydrophobic surface area exposed upon denaturation (delta delta ASAHP). We found only a new correlation between the delta delta G and delta delta ASAHP of all of the hydrophobic residues if the effect of the secondary structure propensity was taken into account. Study holds ProTherm entries: 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 13428, 13429, 13430, 13431, 13432, 13433, 13434, 13435, 13436 Extra Details: human lysozyme; calorimetry; hydrophobic effect; conformational stability;,Gibbs energy; thermodynamic parameters

Submission Details

ID: Qz7qCC2V4

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:16 p.m.

Version: 1

Publication Details
Takano K;Yamagata Y;Fujii S;Yutani K,Biochemistry (1997) Contribution of the hydrophobic effect to the stability of human lysozyme: calorimetric studies and X-ray structural analyses of the nine valine to alanine mutants. PMID:9020766
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
2MEA 1998-05-02T00:00:00+0000 2.2 CHANGES IN CONFORMATIONAL STABILITY OF A SERIES OF MUTANT HUMAN LYSOZYMES AT CONSTANT POSITIONS
1GE4 2000-10-06T00:00:00+0000 1.8 CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT LEFT-HANDED HELICAL POSITIONS
4I0C 2012-11-16T00:00:00+0000 1.95 The structure of the camelid antibody cAbHuL5 in complex with human lysozyme
1GF5 2000-11-30T00:00:00+0000 1.8 BURIED POLAR MUTANT HUMAN LYSOZYME
1LZS 1994-09-14T00:00:00+0000 1.6 STRUCTURAL CHANGES OF THE ACTIVE SITE CLEFT AND DIFFERENT SACCHARIDE BINDING MODES IN HUMAN LYSOZYME CO-CRYSTALLIZED WITH HEXA-N-ACETYL-CHITOHEXAOSE AT PH 4.0
1IP5 2001-04-20T00:00:00+0000 1.8 G105A HUMAN LYSOZYME
2MEB 1998-05-02T00:00:00+0000 1.8 CHANGES IN CONFORMATIONAL STABILITY OF A SERIES OF MUTANT HUMAN LYSOZYMES AT CONSTANT POSITIONS
2MEF 1998-05-04T00:00:00+0000 1.8 CONTRIBUTION OF HYDROPHOBIC EFFECT TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME
2MEI 1998-05-02T00:00:00+0000 1.8 CONTRIBUTION OF HYDROPHOBIC EFFECT TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME
1B5V 1999-01-11T00:00:00+0000 2.17 CONTRIBUTION OF HYDROGEN BONDS TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME: CALORIMETRY AND X-RAY ANALYSIS OF SIX SER->ALA MUTANTS

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
96.9 Lysozyme C P79180 LYSC_HYLLA
99.2 Lysozyme C P79239 LYSC_PONPY
100.0 Lysozyme C P61628 LYSC_PANTR
100.0 Lysozyme C P61627 LYSC_PANPA
100.0 Lysozyme C P61626 LYSC_HUMAN
100.0 Lysozyme C P79179 LYSC_GORGO