Contribution of water molecules in the interior of a protein to the conformational stability.


Abstract

Water molecules frequently occur in the interior of globular proteins. To elucidate the contribution of buried water molecules to the conformational stability of a protein, we examined the crystal structures and the thermodynamic parameters of denaturation of six Ile to Ala/Gly mutant human lysozymes, in which a cavity is created at each mutation site by the substitution of a smaller side-chain for a larger one. One or two ordered water molecules were found in the cavities created in some mutants (I106A, I59A and I59G). The cavity volumes for these three mutants were bigger than those that remained empty in the other mutants. The stability of the mutant proteins with the newly introduced water molecules was about 8 kJ/mol higher than that expected from the change in hydrophobic surface area (DeltaDeltaASAHP) exposed upon denaturation. It was concluded that a water molecule in a cavity created in the interior of a protein contributes favorably to the stability. Study holds ProTherm entries: 3471, 3472, 3473, 3474, 3475, 3476, 3477, 3478, 3479, 3480, 3481, 3482, 3483, 3484, 3485, 3486, 3487, 3488, 3489, 3490, 3491, 3492, 3493, 3494, 3495, 3496, 3497, 3498, 3499, 3500, 3501, 3502, 3503, 3504, 3505, 14234, 14235, 14236, 14237, 14238, 14239, 14240 Extra Details: water molecule; protein stability; cavity;,hydrophobicity; human lysozyme

Submission Details

ID: Y4K4mGqp

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:21 p.m.

Version: 1

Publication Details
Takano K;Funahashi J;Yamagata Y;Fujii S;Yutani K,J. Mol. Biol. (1997) Contribution of water molecules in the interior of a protein to the conformational stability. PMID:9398521
Additional Information

Study Summary

Number of data points 157
Proteins Lysozyme C ; Lysozyme C ; Lysozyme C ; Lysozyme C ; Lysozyme C ; Lysozyme C ; Lysozyme C ; Lysozyme C
Unique complexes 8
Assays/Quantities/Protocols Experimental Assay: dHvH ionic:: , pH:2.49 ; Experimental Assay: dCp pH:2.66, ionic:: ; Experimental Assay: dHcal pH:2.66, ionic:: ; Experimental Assay: ddG ; Experimental Assay: dCp ionic:-: -, pH:2.7, temp:64.9 C ; Experimental Assay: dHcal ionic:-: -, pH:2.7, temp:64.9 C ; Experimental Assay: dHvH ionic:-: -, pH:2.7, temp:64.9 C ; Experimental Assay: dTm ; Experimental Assay: dCp ionic:: , pH:2.7 ; Experimental Assay: dHcal ionic:: , pH:2.7 ; Experimental Assay: Tm pH:2.7 ; Experimental Assay: dHvH ionic:: , pH:2.7 ; Experimental Assay: dCp pH:2.82, ionic:: ; Experimental Assay: dHcal pH:2.82, ionic:: ; Experimental Assay: Tm pH:2.82 ; Experimental Assay: dHvH pH:2.82, ionic:: ; Experimental Assay: dCp ionic:: , pH:3.02 ; Experimental Assay: dHcal ionic:: , pH:3.02 ; Experimental Assay: Tm pH:3.02 ; Experimental Assay: dHvH ionic:: , pH:3.02 ; Experimental Assay: dCp pH:3.16, ionic:: ; Experimental Assay: dHcal pH:3.16, ionic:: ; Experimental Assay: Tm pH:3.16 ; Experimental Assay: dHvH pH:3.16, ionic:: ; Experimental Assay: Tm pH:2.73 ; Experimental Assay: dCp ionic:: , pH:2.51 ; Experimental Assay: dHcal ionic:: , pH:2.51 ; Experimental Assay: Tm pH:2.51 ; Experimental Assay: dHvH ionic:: , pH:2.51 ; Experimental Assay: dCp pH:3.1, ionic:: ; Experimental Assay: dHcal pH:3.1, ionic:: ; Experimental Assay: Tm pH:3.1 ; Experimental Assay: dHvH pH:3.1, ionic:: ; Experimental Assay: dCp ionic:: , pH:2.95 ; Experimental Assay: dHcal ionic:: , pH:2.95 ; Experimental Assay: Tm pH:2.95 ; Experimental Assay: dHvH ionic:: , pH:2.95 ; Experimental Assay: dCp ionic:: , pH:3.09 ; Experimental Assay: dHcal ionic:: , pH:3.09 ; Experimental Assay: Tm pH:3.09 ; Experimental Assay: dHvH ionic:: , pH:3.09 ; Experimental Assay: dCp ionic:: , pH:2.49 ; Experimental Assay: dHcal ionic:: , pH:2.49 ; Experimental Assay: Tm pH:2.49 ; Experimental Assay: Tm pH:2.66 ; Experimental Assay: dHvH pH:2.66, ionic:: ; Experimental Assay: dCp pH:2.8, ionic:: ; Experimental Assay: dHcal pH:2.8, ionic:: ; Experimental Assay: Tm pH:2.8 ; Experimental Assay: dHvH ionic:: , pH:2.8 ; Experimental Assay: dCp pH:2.98, ionic:: ; Experimental Assay: dHcal pH:2.98, ionic:: ; Experimental Assay: Tm pH:2.98 ; Experimental Assay: dHvH pH:2.98, ionic:: ; Experimental Assay: dCp ionic:: , pH:3.12 ; Experimental Assay: dHcal ionic:: , pH:3.12 ; Experimental Assay: Tm pH:3.12 ; Experimental Assay: dHvH ionic:: , pH:3.12 ; Experimental Assay: dCp pH:2.5, ionic:: ; Experimental Assay: dHcal pH:2.5, ionic:: ; Experimental Assay: Tm pH:2.5 ; Experimental Assay: dHvH pH:2.5, ionic:: ; Experimental Assay: dCp pH:2.81, ionic:: ; Experimental Assay: dHcal pH:2.81, ionic:: ; Experimental Assay: Tm pH:2.81 ; Experimental Assay: dHvH pH:2.81, ionic:: ; Experimental Assay: dCp ionic:: , pH:3.08 ; Experimental Assay: dHcal ionic:: , pH:3.08 ; Experimental Assay: Tm pH:3.08 ; Experimental Assay: dHvH ionic:: , pH:3.08 ; Experimental Assay: dCp ionic:: , pH:2.67 ; Experimental Assay: dHcal ionic:: , pH:2.67 ; Experimental Assay: Tm pH:2.67 ; Experimental Assay: dHvH ionic:: , pH:2.67 ; Experimental Assay: dCp ionic:: , pH:2.96 ; Experimental Assay: dHcal ionic:: , pH:2.96 ; Experimental Assay: Tm pH:2.96 ; Experimental Assay: dHvH ionic:: , pH:2.96
Libraries Mutations for sequence KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYNTRATNYNAGDRSTDYGIFQINSRYWCNDGKTPGAVNACHLSCSALLQDNIADAVACAKRVVRDPQGIRAWVAWRNRCQNRDVRQYVQGCGV

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