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Circularly permuted dihydrofolate reductase possesses all the properties of the molten globule state, but can resume functional tertiary structure by interaction with its ligands
Author(s) -
Uversky Vladimir N.,
Protasova Natalya YU.,
Rogov Vladimir V.,
Vassilenko Konstantin S.,
Gudkov Anatoly T.,
Kutyshenko Viktor P.
Publication year - 1996
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560050910
Subject(s) - dihydrofolate reductase , molten globule , protein tertiary structure , chemistry , protein folding , protein secondary structure , protein structure , mutagenesis , folding (dsp implementation) , stereochemistry , biochemistry , enzyme , mutation , gene , electrical engineering , engineering
It is obvious that functional activity of a protein molecule is closely related to its structure. On the other hand, the understanding of structure‐function relationship still remains one of the intriguing problems of molecular biology. There is widespread belief that mutagenesis presents a real way to solve this problem. Following this assumption, we have investigated the effect of circular permutation in dihydrofolate reductase from E. coli on protein structure and functioning. It has been shown that in the absence of ligands two circularly permuted variants of dihydrofolate reductase possess all the properties of the molten globule state. However, after addition of ligands they gain the native‐like structural properties and specific activity. This means that the in vitro folding of permuted dihydrofolate reductase is terminated at the stage of the molten globule formation. Interaction of permuted protein with ligands leads to the structural adjustment and formation of active protein molecules.