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Conversation 11: No. 1

category image Volume: Conversation 11
Issue Number 1
May 2000
ISBN 0-940030-80-2

Contribution of Salt Bridges Toward Protein Thermostability

We present an extensive study of the structural factors suggested to be responsible for thermostability, in 18 nonredundant families of thermophilic and mesophilic proteins. Each of these 18 families consists of homologous thermophile-mesophile pairs, with high resolution crystal structures for both pair-members available in the Protein Data Bank (PDB). We observe that both the thermophilic and the mesophilic proteins have similar hydrophobicities, oligomeric states, and hydrogen bonds. On the other hand, salt bridges increase in most of the thermophilic proteins. Yet, on the other hand, salt bridges have been proposed to destabilize protein structures. Hence, here we seek to understand why do salt bridges occur more frequently in thermophilic proteins. Investigating this problem, we focus on the glutamate dehydrogenase family. Computation of the electrostatic contribution of salt bridge energies by solving the Poisson equation in a continuum solvent medium, shows that the salt bridges in the glutamate dehydrogenase from the hyperthermophile Pyrococcus furiosus are highly stabilizing. In contrast, the salt bridges in the mesophilic Clostridium symbiosum glutamate dehydrogenase contribute only marginally to protein stability. The presence of a larger number of salt bridges cooperatively enhances their strength. Our results indicate that salt bridges and their networks may have an important role in rigidifying the protein structure at high temperatures. Formation of salt bridge networks may help in explaining the increased occurrence and stability of salt bridges in hyperthermophiles.

Sandeep Kumar1
Chung-Jung Tsai2
Buyong Ma2
Ruth Nussinov1,3

1Intramural Research Support Program
SAIC Frederick National Cancer Institute
Cancer Research and Development Center
Laboratory of Experimental and Computational Biology
Bldg 469, Rm 151
Frederick, MD 21702
2 Laboratory of Experimental and Computational Biology
NCI-FCRDC
Bldg 469, Rm 151
Frederick, MD 21702
3Sackler Institute of Molecular Medicine
Sackler School of Medicine
Tel Aviv University
Tel Aviv 69978, Israel

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