Buried water molecules contribute to the conformational stability of a protein.


Abstract

This study sought to attain a better understanding of the contribution of buried water molecules to protein stability. The 3SS human lysozyme lacks one disulfide bond between Cys77 and Cys95 and is significantly destabilized compared with the wild-type human lysozyme (4SS). We examined the structure and stability of the I59A-3SS mutant human lysozyme, in which a cavity is created at the mutation site. The crystal structure of I59A-3SS indicated that there were ordered new water molecules in the cavity created. The stability of I59A-3SS is 5.5 kJ/mol less than that of 3SS. The decreased stability of I59A-3SS (5.5 kJ/mol) is similar to that of Ile to Ala mutants with newly introduced water molecules in other globular proteins (6.3 +/- 2.1 kJ/mol), but is less than that of Ile/Leu to Ala mutants with empty cavities (13.7 +/- 3.1 kJ/mol). This indicates that water molecules partially compensate for the destabilization by decreasing hydrophobic and van der Waals interactions. These results provide further evidence that buried water molecules contribute to protein stability. Study holds ProTherm entries: 16094, 16095, 16096, 16097 Extra Details: cavity; human lysozyme; mutant protein; protein stability; water molecule

Submission Details

ID: Hoc4AnLE4

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:47 p.m.

Version: 1

Publication Details
Takano K;Yamagata Y;Yutani K,Protein Eng. (2003) Buried water molecules contribute to the conformational stability of a protein. PMID:12646687
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
133L 1993-06-01T00:00:00+0000 1.77 ROLE OF ARG 115 IN THE CATALYTIC ACTION OF HUMAN LYSOZYME. X-RAY STRUCTURE OF HIS 115 AND GLU 115 MUTANTS
134L 1993-06-01T00:00:00+0000 1.77 ROLE OF ARG 115 IN THE CATALYTIC ACTION OF HUMAN LYSOZYME. X-RAY STRUCTURE OF HIS 115 AND GLU 115 MUTANTS
1B5U 1999-01-11T00:00:00+0000 1.8 CONTRIBUTION OF HYDROGEN BONDS TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME: CALORIMETRY AND X-RAY ANALYSIS OF SIX SER->ALA MUTANT
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
1B5W 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
1B5X 1999-01-11T00:00:00+0000 2.0 Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and x-ray analysis of six ser->ala mutants
1B5Y 1999-01-11T00:00:00+0000 2.2 CONTRIBUTION OF HYDROGEN BONDS TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME: CALORIMETRY AND X-RAY ANALYSIS OF SIX SER->ALA MUTANTS
1B5Z 1999-01-11T00:00:00+0000 2.2 CONTRIBUTION OF HYDROGEN BONDS TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME: CALORIMETRY AND X-RAY ANALYSIS OF SIX SER->ALA MUTANTS
1B7L 1999-01-24T00:00:00+0000 1.8 VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES
1B7M 1999-01-24T00:00:00+0000 2.2 VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES

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 P79179 LYSC_GORGO
100.0 Lysozyme C P61628 LYSC_PANTR
100.0 Lysozyme C P61627 LYSC_PANPA
100.0 Lysozyme C P61626 LYSC_HUMAN