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Contribution of hydrogen bonds to protein stability
Open accessAbstract
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.
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Citations
Cites
Some Factors in the Interpretation of Protein Denaturation
Kauzmann, W. (1959) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60608-7 · Cited by 4,870
Dominant forces in protein folding
Dill, K. A. (1990) · Biochemistry · doi:10.1021/bi00483a001 · Cited by 3,800
The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain
Pauling, L., Corey, R. B., & Branson, H. R. (1951) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.37.4.205 · Cited by 2,915
[14]Determination and analysis of urea and guanidine hydrochloride denaturation curves
Pace, C. N. (1986) · Methods in Enzymology · doi:10.1016/0076-6879(86)31045-0 · Cited by 2,258
Self-citationMyers, J. K., Nick Pace, C., & Martin Scholtz, J. (1995) · Protein Science · doi:10.1002/pro.5560041020 · Cited by 1,720
Self-citationEnergetics of Protein Structure
(1995) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60548-3 · Cited by 1,065
Hydrogen bonding and biological specificity analysed by protein engineering
Fersht, A. R., Shi, J.-P., Knill-Jones, J., Lowe, D. M., Wilkinson, A. J., Blow, D. M., Brick, P., Carter, P., Waye, M. M. Y., & Winter, G. (1985) · Nature · doi:10.1038/314235a0 · Cited by 1,056
Pauling, L., & Corey, R. B. (1951) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.37.11.729 · Cited by 804
On the Structure of Native, Denatured, and Coagulated Proteins
Mirsky, A. E., & Pauling, L. (1936) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.22.7.439 · Cited by 516
The hydrogen bond in molecular recognition
Fersht, A. R. (1987) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(87)90146-0 · Cited by 467
Contribution of Hydrophobic Interactions to Protein Stability
Pace, C. N., Fu, H., Fryar, K. L., Landua, J., Trevino, S. R., Shirley, B. A., Hendricks, M. M., Iimura, S., Gajiwala, K., Scholtz, J. M., et al. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.02.053 · Cited by 459
Self-citationHydrogen bonding in globular proteins
Stickle, D. F., Presta, L. G., Dill, K. A., & Rose, G. D. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)91058-w · Cited by 408
Protein structure, stability and solubility in water and other solvents
Nick Pace, C., Treviño, S., Prabhakaran, E., & Martin Scholtz, J. (2004) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.2004.1500 · Cited by 393
Serrano, L., Kellis, J. T., Cann, P., Matouschek, A., & Fersht, A. R. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)90562-x · Cited by 382
Pauling, L., & Niemann, C. (1939) · Journal of the American Chemical Society · doi:10.1021/ja01876a065 · Cited by 362
Hydrogen bonding stabilizes globular proteins
Myers, J. K., & Pace, C. N. (1996) · Biophysical Journal · doi:10.1016/s0006-3495(96)79401-8 · Cited by 308
Self-citationLinear extrapolation method of analyzing solvent denaturation curves
Pace, C. N., & Shaw, K. L. (2000) · Proteins: Structure, Function, and Genetics · doi:10.1002/1097-0134(2000)41:4+<1::aid-prot10>3.0.co;2-2 · Cited by 300
Self-citationContribution of hydrogen bonding to the conformational stability of ribonuclease T1
Shirley, B. A., Stanssens, P., Hahn, U., & Pace, C. N. (1992) · Biochemistry · doi:10.1021/bi00118a013 · Cited by 276
Self-citationFree Energy Balance in Protein Folding
(1995) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60331-9 · Cited by 275
Three-dimensional hydrogen-bond geometry and probability information from a crystal survey
Mills, J. E. J., & Dean, P. M. (1996) · Journal of Computer-Aided Molecular Design · doi:10.1007/bf00134183 · Cited by 262
Modest stabilization by most hydrogen-bonded side-chain interactions in membrane proteins
Joh, N. H., Min, A., Faham, S., Whitelegge, J. P., Yang, D., Woods, V. L., & Bowie, J. U. (2008) · Nature · doi:10.1038/nature06977 · Cited by 254
Mrsă, V., Seidl, T., Gentzsch, M., & Tanner, W. (1997) · Yeast · doi:10.1002/(sici)1097-0061(19970930)13:12<1145::aid-yea163>3.0.co;2-y · Cited by 227
A Thermostable 35-Residue Subdomain within Villin Headpiece
McKnight, J. C., Doering, D. S., Matsudaira, P. T., & Kim, P. S. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0387 · Cited by 226
Chiu, T. K., Kubelka, J., Herbst-Irmer, R., Eaton, W. A., Hofrichter, J., & Davies, D. R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502495102 · Cited by 224
Brandts, J. F. (1964) · Journal of the American Chemical Society · doi:10.1021/ja01074a014 · Cited by 216
Gao, J., Bosco, D. A., Powers, E. T., & Kelly, J. W. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1610 · Cited by 212
A new method for determining the heat capacity change for protein folding
Pace, C. N., & Laurents, D. V. (1989) · Biochemistry · doi:10.1021/bi00432a026 · Cited by 197
Self-citationLazaridis, T., Archontis, G., & Karplus, M. (1995) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60547-1 · Cited by 184
Protein folding: from the levinthal paradox to structure prediction
Honig, B. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3006 · Cited by 177
Membrane protein folding: how important are hydrogen bonds?
Bowie, J. U. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.10.003 · Cited by 167
Hydrophobicity of amino acid subgroups in proteins
Lesser, G. J., & Rose, G. D. (1990) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.340080104 · Cited by 162
Tyrosine hydrogen bonds make a large contribution to protein stability
Pace, C. N., Horn, G., Hebert, E. J., Bechert, J., Shaw, K., Urbanikova, L., Scholtz, J. M., & Ševčı́k, J. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4956 · Cited by 156
Self-citationPace, C. N., Hebert, E. J., Shaw, K. L., Schell, D., Both, V., Krajčíková, D., Ševčík, J., Wilson, K. S., Dauter, Z., Hartley, R. W., et al. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1760 · Cited by 148
Self-citationCrystal Structure of Lyme Disease Variable Surface Antigen VlsE of Borrelia burgdorferi
Eicken, C., Sharma, V., Klabunde, T., Lawrenz, M. B., Hardham, J. M., Norris, S. J., & Sacchettini, J. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201547200 · Cited by 147
Polar Group Burial Contributes More to Protein Stability than Nonpolar Group Burial
Pace, C. N. (2000) · Biochemistry · doi:10.1021/bi001574j · Cited by 140
Self-citationProtein stability effects of a complete set of alanine substitutions in Arc repressor
Milla, M. E., Brown, B. M., & Sauer, R. T. (1994) · Nature Structural Biology · doi:10.1038/nsb0894-518 · Cited by 124
Green, S. M., Meeker, A. K., & Shortle, D. (1992) · Biochemistry · doi:10.1021/bi00140a005 · Cited by 120
Loladze, V. V., Ermolenko, D. N., & Makhatadze, G. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00465-5 · Cited by 112
Energetics of protein hydrogen bonds
Pace, C. N. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb0709-681 · Cited by 92
Self-citationAdding backbone to protein folding: why proteins are polypeptides
Honig, B. H., & Cohen, F. E. (1996) · Folding and Design · doi:10.1016/s1359-0278(96)00005-3 · Cited by 84
[24] Evaluating contribution of hydrogen bonding and hydrophobic bonding to protein folding
Pace, C. N. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)59060-9 · Cited by 81
Self-citationEnergetic contribution of side chain hydrogen bonding to the stability of staphylococcal nuclease
Byrne, M. P., Manuel, R., Lowe, L. G., & Stites, W. E. (1995) · Biochemistry · doi:10.1021/bi00042a029 · Cited by 78
Giletto, A., & Pace, C. N. (1999) · Biochemistry · doi:10.1021/bi991422s · Cited by 78
Self-citationHydrogen Bonding Markedly Reduces the pK of Buried Carboxyl Groups in Proteins
Thurlkill, R. L., Grimsley, G. R., Scholtz, J. M., & Pace, C. N. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.07.056 · Cited by 75
Self-citationOn the relative strengths of amide…amide and amide…water hydrogen bonds
Mitchell, J. B. O., & Price, S. L. (1991) · Chemical Physics Letters · doi:10.1016/0009-2614(91)85003-f · Cited by 70
Bunagan, M. R., Gao, J., Kelly, J. W., & Gai, F. (2009) · Journal of the American Chemical Society · doi:10.1021/ja901860f · Cited by 69
Powers, E. T., Deechongkit, S., & Kelly, J. W. (2005) · Advances in protein chemistry · doi:10.1016/s0065-3233(05)72002-7 · Cited by 67
The Contribution of Polar Group Burial to Protein Stability Is Strongly Context-dependent
Takano, K., Scholtz, J. M., Sacchettini, J. C., & Pace, C. N. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304177200 · Cited by 62
Self-citationHebert, E. J., Giletto, A., Ševčı́k, J., Urbanikova, L., Wilson, K. S., Dauter, Z., & Pace, C. N. (1998) · Biochemistry · doi:10.1021/bi9815243 · Cited by 59
Self-citationPurification of Ribonucleases Sa, Sa2, and Sa3 after Expression inEscherichia coli
Hebert, E. J., Grimsley, G. R., Hartley, R. W., Horn, G., Schell, D., Garcia, S., Both, V., Ševčík, J., & Pace, C. N. (1997) · Protein Expression and Purification · doi:10.1006/prep.1997.0776 · Cited by 58
Self-citationTakano, K., Yamagata, Y., Kubota, M., Funahashi, J., Fujii, S., & Yutani, K. (1999) · Biochemistry · doi:10.1021/bi9901228 · Cited by 57
Self-citationRational modification of protein stability by targeting surface sites leads to complicated results
Xiao, S., Patsalo, V., Shan, B., Bi, Y., Green, D. F., & Raleigh, D. P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222245110 · Cited by 57
Yamagata, Y., Kubota, M., Sumikawa, Y., Funahashi, J., Takano, K., Fujii, S., & Yutani, K. (1998) · Biochemistry · doi:10.1021/bi980431i · Cited by 52
Self-citationPace, C. N., Huyghues‐Despointes, B. M. P., Fu, H., Takano, K., Scholtz, J. M., & Grimsley, G. R. (2010) · Protein Science · doi:10.1002/pro.370 · Cited by 47
Self-citationHydrogen bonding increases packing density in the protein interior
Schell, D., Tsai, J. W., Scholtz, J. M., & Pace, C. N. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20826 · Cited by 47
Self-citationXiao, S., Bi, Y., Shan, B., et al. (2009) · Biochemistry · doi:10.1021/bi8021763 · Cited by 33
Campos, L. A., Cuesta‐López, S., López-Llano, J., Falo, F., & Sancho, J. (2004) · Biophysical Journal · doi:10.1529/biophysj.104.050203 · Cited by 23
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Rocklin, G. J., Chidyausiku, T. M., Goreshnik, I., Ford, A., Houliston, S., Lemak, A., Carter, L., Ravichandran, R., Mulligan, V. K., Chevalier, A., et al. (2017) · Science · doi:10.1126/science.aan0693 · Cited by 501
Aggregate Science: From Structures to Properties
Zhang, H., Zhao, Z., Turley, A. T., Wang, L., McGonigal, P. R., Tu, Y., Li, Y., Wang, Z., Kwok, R. T. K., Lam, J. W. Y., et al. (2020) · Advanced Materials · doi:10.1002/adma.202001457 · Cited by 518
Nick Pace, C., Scholtz, J. M., & Grimsley, G. R. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.05.006 · Cited by 386
Self-citationAli, A., & Ahmed, S. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b01052 · Cited by 304
Hossain, M. M., Adhikari, J., Dutta, A., Khandaker, A., Islam, S., Rahman, M. M., & Shibly, A. Z. (2025) · PLOS One · doi:10.1371/journal.pone.0331339 · Cited by 11
Metadata
- Authors
- Pace, C. N., Fu, H., Lee Fryar, K., Landua, J., Trevino, S. R., Schell, D., Thurlkill, R. L., Imura, S., Scholtz, J. M., Gajiwala, K., Sevcik, J., Urbanikova, L., Myers, J. K., Takano, K., Hebert, E. J., Shirley, B. A., & Grimsley, G. R.
- Venue
- Protein Science
- Publisher
- Wiley
- Published
- 2014-03-25
- Volume
- 23
- Issue
- 5
- Pages
- 652-661
- ISSN
- 0961-8368 (ISSN-L)
- 1469-896X
- OpenAlex
- W2130086970
- Cited by
- 599
- References
- 57
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- bronze
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