Bioinformatic method for protein thermal stabilization by structural entropy optimization.
Abstract
Engineering proteins for higher thermal stability is an important and difficult challenge. We describe a bioinformatic method incorporating sequence alignments to redesign proteins to be more stable through optimization of local structural entropy. Using this method, improved configurational entropy (ICE), we were able to design more stable variants of a mesophilic adenylate kinase with only the sequence information of one psychrophilic homologue. The redesigned proteins display considerable increases in their thermal stabilities while still retaining catalytic activity. ICE does not require a three-dimensional structure or a large number of homologous sequences, indicating a broad applicability of this method. Our results also highlight the importance of entropy in the stability of protein structures. Study holds ProTherm entries: 24676, 24677, 24678 Extra Details: adenylate kinase; improved configurational entropy; local structural entropy; protein engineering; protein stability
Submission Details
ID: jG9UmvwW3
Submitter: Connie Wang
Submission Date: April 24, 2018, 8:55 p.m.
Version: 1
Publication Details
Bae E;Bannen RM;Phillips GN,Proc. Natl. Acad. Sci. U.S.A. (2008) Bioinformatic method for protein thermal stabilization by structural entropy optimization. PMID:18621726Additional Information
Study Summary
| Number of data points | 3 |
| Proteins | Adenylate kinase ; Adenylate kinase |
| Unique complexes | 3 |
| Assays/Quantities/Protocols | Experimental Assay: dTm |
| Libraries | Mutations for sequence MNLVLMGLPGAGKGTQGERIVEDYGIPHISTGDMFRAAMKEETPLGLEAKSYIDKGELVPDEVTIGIVKERLGKDDCERGFLLDGFPRTVAQAEALEEILEEYGKPIDYVINIEVDKDVLMERLTGRRICSVCGTTYHLVFNPPKTPGICDKDGGELYQRADDNEETVSKRLEVNMKQTQPLLDFYSEKGYLANVNGQQDIQDVYADVKDLLGGLKK |
Structure view and single mutant data analysis
Study data
| 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 |
|---|---|---|---|
| 4QBG | 2014-06-25 | 1.37 | Crystal structure of a stable adenylate kinase variant AKlse4 |
| 4MKG | 2014-03-26 | 1.45 | Crystal structure of a stable adenylate kinase variant AKv8 |
| 4MKH | 2014-03-26 | 1.5 | Crystal structure of a stable adenylate kinase variant AKv18 |
| 3DL0 | 2009-06-09 | 1.58 | Crystal structure of adenylate kinase variant AKlse3 |
| 4TYQ | 2014-11-26 | 1.65 | Crystal structure of an adenylate kinase mutant--AKm2 |
| 4MKF | 2014-03-26 | 1.7 | Crystal structure of a stable adenylate kinase variant AKv3 |
| 4QBF | 2014-06-25 | 1.8 | Crystal structure of a stable adenylate kinase variant AKlse2 |
| 2P3S | 2008-01-22 | 1.8 | Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (G214R/Q199R) |
| 2OSB | 2008-01-15 | 1.8 | Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (Q16L/Q199R/) |
| 2EU8 | 2006-06-27 | 1.8 | Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (Q199R) |
| 2QAJ | 2008-04-29 | 1.8 | Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (Q199R/G213E) |
| 2ORI | 2008-01-15 | 1.8 | Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (A193V/Q199R/) |
| 2OO7 | 2008-02-05 | 1.8 | Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (T179I/Q199R) |
| 3DKV | 2009-06-09 | 1.82 | Crystal structure of adenylate kinase variant AKlse1 |
| 1P3J | 2004-05-04 | 1.9 | Adenylate Kinase from Bacillus subtilis |
| 5X6I | 2018-02-28 | 2.0 | Crystal structure of B. subtilis adenylate kinase variant |
| 4TYP | 2014-11-26 | 2.9 | Crystal structure of an adenylate kinase mutant--AKm1 |