Side-chain determinants of beta-sheet stability.


Abstract

beta-Sheet propensities of different amino acids depend on the context of both secondary and tertiary structure. In an attempt to establish general empirical relationships that determine this context dependence, we have determined the free energy of unfolding of a series of mutants at six positions in the beta-sheet of chymotrypsin inhibitor 2 (CI2). We have generated the series Val-->Ala-->Gly and Val<==>Thr at five positions, as well as the side-chain deletion Ile-->Val at residue 49 and Ala-->Gly at residue 77. In the series Val-->Ala-->Gly, the ranking order in terms of stability is Val > Ala > Gly at all positions. However, the change in free energy on deletion of methylene groups varies greatly. When Val and Thr are interchanged, the wild-type residue is always the more stable, but by a different amount at each position. We have attempted to rationalize the data by relating it to changes in solvent-accessible surface area, packing density, and statistically derived pseudo-energy functions that depend on phi, psi angles. There is no significant correlation of the energies with any of the variables except with the pseudo-energy function, but the deviations from these values are large. We conclude that thermodynamic scales for beta-sheet propensity are currently of insufficient precision for general design purposes, although they may be useful in special cases. Study holds ProTherm entries: 1873, 1874, 1875, 1876, 1877, 1878, 1879, 1880, 1881, 1882, 1883, 1884, 1885, 1886, 1887, 1888, 1889, 1890 Extra Details:

Submission Details

ID: Y3asuvE94

Submitter: Connie Wang

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

Version: 1

Publication Details
Otzen DE;Fersht AR,Biochemistry (1995) Side-chain determinants of beta-sheet stability. PMID:7727432
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
1CIS 1993-04-23T00:00:00+0000 0 CONTEXT DEPENDENCE OF PROTEIN SECONDARY STRUCTURE FORMATION. THE THREE-DIMENSIONAL STRUCTURE AND STABILITY OF A HYBRID BETWEEN CHYMOTRYPSIN INHIBITOR 2 AND HELIX E FROM SUBTILISIN CARLSBERG
1CIR 1995-10-02T00:00:00+0000 0 COMPLEX OF TWO FRAGMENTS OF CI2 [(1-40)(DOT)(41-64)]
1CIR 1995-10-02T00:00:00+0000 0 COMPLEX OF TWO FRAGMENTS OF CI2 [(1-40)(DOT)(41-64)]
1CIQ 1995-10-02T00:00:00+0000 2.2 COMPLEX OF TWO FRAGMENTS OF CI2, RESIDUES 1-40 AND 41-64
1CIQ 1995-10-02T00:00:00+0000 2.2 COMPLEX OF TWO FRAGMENTS OF CI2, RESIDUES 1-40 AND 41-64
1YPA 1993-01-10T00:00:00+0000 2.0 DIRECT OBSERVATION OF BETTER HYDRATION AT THE N-TERMINUS OF AN ALPHA-HELIX WITH GLYCINE RATHER THAN ALANINE AS N-CAP
3CI2 1991-09-10T00:00:00+0000 0 REFINEMENT OF THE THREE-DIMENSIONAL SOLUTION STRUCTURE OF BARLEY SERINE PROTEINASE INHIBITOR 2 AND COMPARISON WITH THE STRUCTURES IN CRYSTALS
2SNI 1988-09-05T00:00:00+0000 2.1 STRUCTURAL COMPARISON OF TWO SERINE PROTEINASE-PROTEIN INHIBITOR COMPLEXES. EGLIN-C-SUBTILISIN CARLSBERG AND CI-2-SUBTILISIN NOVO
1YPB 1993-01-10T00:00:00+0000 2.0 DIRECT OBSERVATION OF BETTER HYDRATION AT THE N-TERMINUS OF AN ALPHA-HELIX WITH GLYCINE RATHER THAN ALANINE AS N-CAP
1YPC 1993-01-10T00:00:00+0000 1.7 DIRECT OBSERVATION OF BETTER HYDRATION AT THE N-TERMINUS OF AN ALPHA-HELIX WITH GLYCINE RATHER THAN ALANINE AS N-CAP

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
92.6 Subtilisin-chymotrypsin inhibitor-2A P08626 ICI3_HORVU
100.0 Subtilisin-chymotrypsin inhibitor-2A P01053 ICI2_HORVU