Role of proline residues in human lysozyme stability: a scanning calorimetric study combined with X-ray structure analysis of proline mutants.


It has been shown that protein stability can be modulated from site-directed mutations that affect the entropy of protein unfolding [Matthews, B. W., Nicholson, H., & Becktel, W. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 6663-6667]. However, the effect of a specific amino acid replacement on stability highly depends on the location of the mutation site and its environment in the protein structure [Yutani, K., Hayashi, S., Sugisaki, Y., & Ogasahara, K. (1991) Proteins Struct., Funct., Genet. 9, 90-98). To clarify the role of specific proline residues in the thermostability of human lysozyme (h-lysozyme), a series of proline mutants were investigated by means of scanning calorimetry and high-resolution X-ray crystallography. The thermodynamic properties of the mutant and wild-type h-lysozymes are compared and discussed on the basis of their three-dimensional structure. h-Lysozyme contains two proline residues at positions 71 and 103. The Pro71----Gly substitution was found to destabilize h-lysozyme by decreasing the entropic contribution of unfolding by about 2 kcal/mol at 68.8 degrees C. This is consistent with the theoretical expectations for such a substitution. However, the same substitution at position 103 (Pro103----Gly) does not affect h-lysozyme stability, and the thermodynamic properties of the P71G/P103G and P71G mutants are essentially the same. Pro71 which is conserved among lysozymes from other species, appears to be important for stability, whereas Pro103, which is not conserved, does not. These differences are explained in terms of residue accessibility to the solvent and crystallographic B-factor, which reflects the amino acid mobility.(ABSTRACT TRUNCATED AT 250 WORDS) Study holds ProTherm entries: 2130, 2131, 2132, 2133, 2134, 2135, 2136, 13927, 13928, 13929, 13930, 13931, 13932, 13933 Extra Details: human lysozyme; proline; protein stability; accessibility;,site-directed mutations; protein structure

Submission Details

ID: zAu8M2Z6

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:18 p.m.

Version: 1

Publication Details
Herning T;Yutani K;Inaka K;Kuroki R;Matsushima M;Kikuchi M,Biochemistry (1992) Role of proline residues in human lysozyme stability: a scanning calorimetric study combined with X-ray structure analysis of proline mutants. PMID:1643041
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 UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Lysozyme C P79179 LYSC_GORGO
100.0 Lysozyme C P61626 LYSC_HUMAN
100.0 Lysozyme C P61627 LYSC_PANPA
100.0 Lysozyme C P61628 LYSC_PANTR
100.0 Lysozyme C P79239 LYSC_PONPY
97.7 Lysozyme C P79180 LYSC_HYLLA
90.8 Lysozyme C P61633 LYSC_CHLAE
90.8 Lysozyme C P61634 LYSC_ERYPA