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:18621726
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
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
2QAJ 2008-04-29 1.8 Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (Q199R/G213E)
2EU8 2006-06-27 1.8 Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (Q199R)
2P3S 2008-01-22 1.8 Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (G214R/Q199R)
2OO7 2008-02-05 1.8 Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (T179I/Q199R)
2OSB 2008-01-15 1.8 Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (Q16L/Q199R/)
2ORI 2008-01-15 1.8 Crystal structure of a thermostable mutant of Bacillus subtilis Adenylate Kinase (A193V/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

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
95.4 Adenylate kinase A7Z0Q9 KAD_BACVZ
100.0 Adenylate kinase P16304 KAD_BACSU