Selected mutations in a mesophilic cytochrome c confer the stability of a thermophilic counterpart.


Mesophilic cytochrome c(551) of Pseudomonas aeruginosa (PA c(551)) became as stable as its thermophilic counterpart, Hydrogenobacter thermophilus cytochrome c(552) (HT c(552)), through only five amino acid substitutions. The five residues, distributed in three spatially separated regions, were selected and mutated with reference to the corresponding residues in HT c(552) through careful structure comparison. Thermodynamic analysis indicated that the stability of the quintuple mutant of PA c(551) could be partly attained through an enthalpic factor. The solution structure of the mutant showed that, as in HT c(552), there were tighter side chain packings in the mutated regions. Furthermore, the mutant had an increased total accessible surface area, resulting in great negative hydration free energy. Our results provide a novel example of protein stabilization in that limited amino acid substitutions can confer the overall stability of a natural highly thermophilic protein upon a mesophilic molecule. Study holds ProTherm entries: 9769, 9770, 9771, 9772, 9773, 9774, 14512, 14513 Extra Details: mesophilic; thermophilic; structure comparison; quintuple mutant;,side chain packings; hydration free energy

Submission Details

ID: QqeaeiF7

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:38 p.m.

Version: 1

Publication Details
Hasegawa J;Uchiyama S;Tanimoto Y;Mizutani M;Kobayashi Y;Sambongi Y;Igarashi Y,J. Biol. Chem. (2000) Selected mutations in a mesophilic cytochrome c confer the stability of a thermophilic counterpart. PMID:10918067
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 Cytochrome c-552 P15452 CY552_HYDTT
100.0 Cytochrome c-551 P00099 CY551_PSEAE