Long-range dynamic effects of point mutations propagate through side chains in the serine protease inhibitor eglin c.


Abstract

Long-range interactions are fundamental to protein behaviors such as cooperativity and allostery. In an attempt to understand the role protein flexibility plays in such interactions, the distribution of local fluctuations in a globular protein was monitored in response to localized, nonelectrostatic perturbations. Two valine-to-alanine mutations were introduced into the small serine protease inhibitor eglin c, and the (15)N and (2)H NMR spin relaxation properties of these variants were analyzed in terms of the Lipari-Szabo dynamics formalism and compared to those of the wild type. Significant changes in picosecond to nanosecond dynamics were observed in side chains located as much as 13 A from the point of mutation. Additionally, those residues experiencing altered dynamics appear to form contiguous surfaces within the protein. In the case of V54A, the large-to-small mutation results in a rigidification of connected residues, even though this mutation decreases the global stability. These findings suggest that dynamic perturbations arising from single mutations may propagate away from the perturbed site through networks of interacting side chains. That this is observed in eglin c, a classically nonallosteric protein, suggests that such behavior will be observed in many, if not all, globular proteins. Differences in behavior between the two mutants suggest that dynamic responses will be context-dependent. Study holds ProTherm entries: 18378, 18379, 18380, 18381, 18382, 18383, 18384, 18385 Extra Details: long-range interactions; flexibility; nonelectrostatic perturbations; context-dependent

Submission Details

ID: AUUeRHVq

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:50 p.m.

Version: 1

Publication Details
Clarkson MW;Lee AL,Biochemistry (2004) Long-range dynamic effects of point mutations propagate through side chains in the serine protease inhibitor eglin c. PMID:15449934
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
1ACB 1991-11-08T00:00:00+0000 2.0 CRYSTAL AND MOLECULAR STRUCTURE OF THE BOVINE ALPHA-CHYMOTRYPSIN-EGLIN C COMPLEX AT 2.0 ANGSTROMS RESOLUTION
1CSE 1988-06-03T00:00:00+0000 1.2 THE HIGH-RESOLUTION X-RAY CRYSTAL STRUCTURE OF THE COMPLEX FORMED BETWEEN SUBTILISIN CARLSBERG AND EGLIN C, AN ELASTASE INHIBITOR FROM THE LEECH HIRUDO MEDICINALIS. STRUCTURAL ANALYSIS, SUBTILISIN STRUCTURE AND INTERFACE GEOMETRY
1EGL 1993-09-03T00:00:00+0000 0 THE SOLUTION STRUCTURE OF EGLIN C BASED ON MEASUREMENTS OF MANY NOES AND COUPLING CONSTANTS AND ITS COMPARISON WITH X-RAY STRUCTURES
1EGP 1995-09-01T00:00:00+0000 2.0 PROTEINASE INHIBITOR EGLIN C WITH HYDROLYSED REACTIVE CENTER
1EGP 1995-09-01T00:00:00+0000 2.0 PROTEINASE INHIBITOR EGLIN C WITH HYDROLYSED REACTIVE CENTER
1MEE 1991-04-15T00:00:00+0000 2.0 THE COMPLEX BETWEEN THE SUBTILISIN FROM A MESOPHILIC BACTERIUM AND THE LEECH INHIBITOR EGLIN-C
1SBN 1991-12-20T00:00:00+0000 2.1 REFINED CRYSTAL STRUCTURES OF SUBTILISIN NOVO IN COMPLEX WITH WILD-TYPE AND TWO MUTANT EGLINS. COMPARISON WITH OTHER SERINE PROTEINASE INHIBITOR COMPLEXES
1SIB 1993-08-02T00:00:00+0000 2.4 REFINED CRYSTAL STRUCTURES OF SUBTILISIN NOVO IN COMPLEX WITH WILD-TYPE AND TWO MUTANT EGLINS. COMPARISON WITH OTHER SERINE PROTEINASE INHIBITOR COMPLEXES
1TEC 1989-05-24T00:00:00+0000 2.2 CRYSTALLOGRAPHIC REFINEMENT BY INCORPORATION OF MOLECULAR DYNAMICS. THE THERMOSTABLE SERINE PROTEASE THERMITASE COMPLEXED WITH EGLIN-C
2SEC 1988-09-05T00:00:00+0000 1.8 STRUCTURAL COMPARISON OF TWO SERINE PROTEINASE-PROTEIN INHIBITOR COMPLEXES. EGLIN-C-SUBTILISIN CARLSBERG AND CI-2-SUBTILISIN NOVO

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 E Chymotrypsinogen A P00766 CTRA_BOVIN
100.0 I Chymotrypsinogen A P01051 ICIC_HIRME