Minimization of cavity size ensures protein stability and folding: structures of Phe46-replaced bovine pancreatic RNase A.


The Phe46 residue, located in the hydrophobic core of RNase A, was replaced with other hydrophobic residues, leucine, valine, or alanine, and their X-ray crystallographic structures were determined up to 1.50-1.80 A resolution in an attempt to examine the relationship between structural changes and conformational stability or folding kinetics. The backbone structure of F46L, F46V, and F46A was indistinguishable from that of the wild-type enzyme, retaining the correct active site structure. However, one water molecule was included in the hydrophobic core of F46A, forming two hydrogen bonds with the backbone peptide chain. The side chain of Met29 in F46V and F46A adopted two different conformations in an equal occupancy. A trapped water molecule and two conformations of Met29 represent changes that minimize the cavity volume. Nevertheless, the replacement of Phe46 with the above residues resulted in a marked decrease in both thermal stability and folding reaction. Thus, Phe46 ensures the thermal stability and the rapid and correct folding of RNase A by the role it plays in forming a highly packed, hydrophobic core. Study holds ProTherm entries: 16627, 16628, 16629, 16630, 16631, 16632, 16633, 16634 Extra Details: hydrophobic core; folding kinetics; active site; cavity volume

Submission Details

ID: JzN9vCCd3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:48 p.m.

Version: 1

Publication Details
Kadonosono T;Chatani E;Hayashi R;Moriyama H;Ueki T,Biochemistry (2003) Minimization of cavity size ensures protein stability and folding: structures of Phe46-replaced bovine pancreatic RNase A. PMID:12962489
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 Ribonuclease pancreatic P61824 RNAS1_BISBI
100.0 Ribonuclease pancreatic P61823 RNAS1_BOVIN
96.8 Ribonuclease pancreatic P67926 RNAS1_CAPHI
96.8 Ribonuclease pancreatic P67927 RNAS1_SHEEP
95.2 Ribonuclease pancreatic P00657 RNAS1_BUBBU
96.0 Ribonuclease pancreatic P07847 RNAS1_AEPME
93.5 Ribonuclease pancreatic P07848 RNAS1_EUDTH
95.2 Ribonuclease pancreatic P00660 RNAS1_CONTA
92.7 Ribonuclease pancreatic P00668 RNAS1_ANTAM
90.3 Ribonuclease pancreatic P00662 RNAS1_GIRCA
96.0 Ribonuclease pancreatic Q29606 RNAS1_ORYLE