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The hydrophobic lock‐and‐key intersubunit motif of glutathione transferase A1‐1: implications for catalysis, ligandin function and stability
Author(s) -
Sayed Yasien,
Wallace Louise A.,
Dirr Heini W.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01747-0
Subject(s) - chemistry , protein subunit , mutant , stereochemistry , dimer , protein structure , glutathione , protein quaternary structure , docking (animal) , active site , serine , protein–protein interaction , biochemistry , biophysics , enzyme , biology , medicine , nursing , organic chemistry , gene
A hydrophobic lock‐and‐key intersubunit motif involving a phenylalanine is a major structural feature conserved at the dimer interface of classes alpha, mu and pi glutathione transferases. In order to determine the contribution of this subunit interaction towards the function and stability of human class alpha GSTA1‐1, the interaction was truncated by replacing the phenylalanine ‘key’ Phe‐51 with serine. The F51S mutant protein is dimeric with a native‐like core structure indicating that Phe‐51 is not essential for dimerization. The mutation impacts on catalytic and ligandin function suggesting that tertiary structural changes have occurred at/near the active and non‐substrate ligand‐binding sites. The active site appears to be disrupted mainly at the glutathione‐binding region that is adjacent to the lock‐and‐key intersubunit motif. The F51S mutant displays enhanced exposure of hydrophobic surface and ligandin function. The lock‐and‐key motif stabilizes the quaternary structure of hGSTA1‐1 at the dimer interface and the protein concentration dependence of stability indicates that the dissociation and unfolding processes of the mutant protein remain closely coupled.