A partially buried site in homologous HPr proteins is not optimized for stability

Eric M Nicholson; Ronald W Peterson; J Martin Scholtz

doi:10.1016/S0022-2836(02)00630-7

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A partially buried site in homologous HPr proteins is not optimized for stability

Journal article

Peer reviewed

A partially buried site in homologous HPr proteins is not optimized for stability

Eric M Nicholson, Ronald W Peterson and J Martin Scholtz

Journal of molecular biology, Vol.321(2), pp.355-362

08/09/2002

DOI: 10.1016/S0022-2836(02)00630-7

PMID: 12144791

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Abstract

The energetic consequences of site-specific replacement of a residue at a partially buried site in the two homologous HPr proteins from Escherichia coli and Bacillus subtilis is described. We determined previously that the replacement of a partially buried Lys residue with Glu at position 49 in E.coli HPr increased the conformational stability of the protein substantially because the side-chain of the latter residue could act as a hydrogen-bond acceptor. Here, we extend this analysis to other side-chains with different chemical properties and abilities to form hydrogen bonds to compare the properties of this position in the backgrounds of two different homologous HPr proteins. We find that the variants with polar residues that can form a tertiary hydrogen bond with a nearby site in the protein are more stable than either hydrophobic residues or polar residues that become buried yet are incapable of forming a new hydrogen bond. Furthermore, the protein with the wild-type residue in each HPr variant is not among the most stable of the proteins studied. These results suggest a general strategy for designing variants in which the overall stability of a protein can be modulated in a defined fashion.

Amino Acid Substitution - genetics

Bacillus subtilis - chemistry

Bacillus subtilis - genetics

Bacterial Proteins

Binding Sites

Escherichia coli - chemistry

Escherichia coli - genetics

Escherichia coli Proteins - chemistry

Escherichia coli Proteins - genetics

Escherichia coli Proteins - metabolism

Hot Temperature

Hydrogen Bonding

Hydrophobic and Hydrophilic Interactions

Models, Molecular

Phosphoenolpyruvate Sugar Phosphotransferase System - chemistry

Phosphoenolpyruvate Sugar Phosphotransferase System - genetics

Phosphoenolpyruvate Sugar Phosphotransferase System - metabolism

Protein Conformation - drug effects

Protein Denaturation - drug effects

Protein Folding

Sequence Homology, Amino Acid

Thermodynamics

Urea - pharmacology

Details

Title: Subtitle: A partially buried site in homologous HPr proteins is not optimized for stability
Creators: Eric M Nicholson - Texas A&M University
Ronald W Peterson - Texas A&M University
J Martin Scholtz - Texas A&M University
Resource Type: Journal article
Publication Details: Journal of molecular biology, Vol.321(2), pp.355-362
DOI: 10.1016/S0022-2836(02)00630-7
PMID: 12144791
ISSN: 0022-2836
eISSN: 1089-8638
Grant note: GM 52483 / NIGMS NIH HHS T32-GM0853 / NIGMS NIH HHS
Language: English
Date published: 08/09/2002
Academic Unit: Research Administration; Pharmaceutical Sciences and Experimental Therapeutics; Biochemistry and Molecular Biology; Chemistry
Record Identifier: 9984293074302771

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