Contribution of hydrogen bonds to protein stability

C Nick Pace; Hailong Fu; Katrina Lee Fryar; John Landua; Saul R Trevino; David Schell; Richard L Thurlkill; Satoshi Imura; J Martin Scholtz; Ketan Gajiwala; Jozef Sevcik; Lubica Urbanikova; Jeffery K Myers; Kazufumi Takano; Eric J Hebert; Bret A Shirley; Gerald R Grimsley

doi:10.1002/pro.2449

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Contribution of hydrogen bonds to protein stability

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Contribution of hydrogen bonds to protein stability

C Nick Pace, Hailong Fu, Katrina Lee Fryar, John Landua, Saul R Trevino, David Schell, Richard L Thurlkill, Satoshi Imura, J Martin Scholtz, Ketan Gajiwala, …

Protein science, Vol.23(5), pp.652-661

03/25/2014

DOI: 10.1002/pro.2449

PMCID: PMC4005716

PMID: 24591301

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Abstract

Our goal was to gain a better understanding of the contribution of the burial of polar groups and their hydrogen bonds to the conformational stability of proteins. We measured the change in stability, Δ(Δ G ), for a series of hydrogen bonding mutants in four proteins: villin headpiece subdomain (VHP) containing 36 residues, a surface protein from Borrelia burgdorferi (VlsE) containing 341 residues, and two proteins previously studied in our laboratory, ribonucleases Sa (RNase Sa) and T1 (RNase T1). Crystal structures were determined for three of the hydrogen bonding mutants of RNase Sa: S24A, Y51F, and T95A. The structures are very similar to wild type RNase Sa and the hydrogen bonding partners form intermolecular hydrogen bonds to water in all three mutants. We compare our results with previous studies of similar mutants in other proteins and reach the following conclusions. (1) Hydrogen bonds contribute favorably to protein stability. (2) The contribution of hydrogen bonds to protein stability is strongly context dependent. (3) Hydrogen bonds by side chains and peptide groups make similar contributions to protein stability. (4) Polar group burial can make a favorable contribution to protein stability even if the polar groups are not hydrogen bonded. (5) The contribution of hydrogen bonds to protein stability is similar for VHP, a small protein, and VlsE, a large protein.

conformational entropy

hydrogen bonds

hydrophobic bonds

large proteins

protein stability

small proteins

Details

Title: Subtitle: Contribution of hydrogen bonds to protein stability
Creators: C Nick Pace - Texas A&M Health Science Center
Hailong Fu - Texas A&M University
Katrina Lee Fryar - Texas A&M Health Science Center
John Landua - Texas A&M Health Science Center
Saul R Trevino - Houston Christian University
David Schell - Texas A&M University
Richard L Thurlkill - University of Louisiana at Monroe
Satoshi Imura - Texas A&M Health Science Center
J Martin Scholtz - Texas A&M Health Science Center
Ketan Gajiwala - Pfizer (United States)
Jozef Sevcik - Slovak Academy of Sciences
Lubica Urbanikova - Slovak Academy of Sciences
Jeffery K Myers - Davidson College
Kazufumi Takano - Kyoto Prefectural University
Eric J Hebert - AbbVie (United States)
Bret A Shirley - Receptos Inc. San Diego California
Gerald R Grimsley - Texas A&M Health Science Center
Resource Type: Journal article
Publication Details: Protein science, Vol.23(5), pp.652-661
DOI: 10.1002/pro.2449
PMID: 24591301
PMCID: PMC4005716
NLM abbreviation: Protein Sci
ISSN: 0961-8368
eISSN: 1469-896X
Publisher: Wiley-Blackwell
Language: English
Date published: 03/25/2014
Academic Unit: Research Administration; Pharmaceutical Sciences and Experimental Therapeutics; Biochemistry and Molecular Biology; Chemistry
Record Identifier: 9984288727302771

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