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  Metastable water clusters in the nonpolar cavities of the thermostable protein tetrabrachion

Yin, H., Hummer, G., & Rasaiah, J. C. (2007). Metastable water clusters in the nonpolar cavities of the thermostable protein tetrabrachion. Journal of the American Chemical Society, 129(23), 7369-7377. doi:10.1021/ja070456h.

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 Creators:
Yin, Hao1, Author
Hummer, Gerhard2, Author                 
Rasaiah, Jayendran C.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA, ou_persistent22              

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Free keywords: Bacterial Proteins, Computer Simulation, Crystallography, X-Ray, Macromolecular Substances, Models, Molecular, Protein Folding, Temperature, Water
 Abstract: Water expulsion from the protein core is a key step in protein folding. Nevertheless, unusually large water clusters confined into the nonpolar cavities have been observed in the X-ray crystal structures of tetrabrachion, a bacterial protein that is thermostable up to at least 403 K (130 degrees C). Here, we use molecular dynamics (MD) simulations to investigate the structure and thermodynamics of water filling the largest cavity of the right-handed coiled-coil stalk of tetrabrachion at 365 K (92 degrees C), the temperature of optimal bacterial growth, and at room temperature (298 K). Hydrogen-bonded water clusters of seven to nine water molecules are found to be thermodynamically stable in this cavity at both temperatures, confirming the X-ray studies. Stability, as measured by the transfer free energy of the optimal size cluster, decreases with increasing temperature. Water filling is thus driven by the energy of transfer and opposed by the transfer entropy, both depending only weakly on temperature. Our calculations suggest that cluster formation becomes unfavorable at approximately 384 K (110 degrees C), signaling the onset of drying just slightly above the temperature of optimal growth. "Drying" thus precedes protein denaturation. At room temperature, the second largest cavity in tetrabrachion accommodates a five water molecule cluster, as reported in the X-ray studies. However, the simulations show that at 365 K the cluster is unstable and breaks up. We suggest that the large hydrophobic cavities may act as binding sites for two proteases, possibly explaining the unusual thermostability of the resulting protease-stalk complexes (up to approximately 393 K, 120 degrees C).

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Language(s): eng - English
 Dates: 2007-01-262007-05-182007-06-13
 Publication Status: Issued
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1021/ja070456h
BibTex Citekey: yin_metastable_2007
 Degree: -

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Title: Journal of the American Chemical Society
  Other : JACS
  Abbreviation : J. Am. Chem. Soc.
Source Genre: Journal
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Publ. Info: Washington, DC : American Chemical Society
Pages: - Volume / Issue: 129 (23) Sequence Number: - Start / End Page: 7369 - 7377 Identifier: ISSN: 0002-7863
CoNE: https://pure.mpg.de/cone/journals/resource/954925376870