PMID: 39646Jul 1, 1979

The effects of chemical modification on the refolding transition of alpha-chymotrypsin

Biophysical Chemistry
J D Stoesz, R Lumry

Abstract

The role of several active site residues of alpha-chymotrypsin in the prototypical refolding transition between active and inactive forms of this enzyme is examined using chemical modification. Oxidation of Met-192 to the sulfoxide results in a derivative which remains entirely in an active state from pH 6 to 9. The derivative becomes inactive only at high pH with pKa = 10.3, delta H0 = 9.5 kcal and delta S0 = -15 eu., indicating the sulfoxide group supplies about 2.1 kcal of active state stabilization relative to the unoxidized methionine side chain. The refolding transition of N-methyl-His-57-alpha-chymotrypsin, in which a nitrogen of the "charge relay" histidine is methylated, displays one ionization process with an apparent pKa of 9.45. The absence of an additional ionization process with a pKa near 7 provides evidence that one of the ionizations in the six state mechanism which describes this transition in alpha-chymotrypsin is linked to the charge relay system. We also demonstrate, using alpha-chymotrypsin, Met-192-sulfoxide-alpha-chymotrypsin and N-methyl-His-57-alpha-chymotrypsin, that the 230 nm circular dichroism band is a quantitative probe of the active-inactive equilibrium, although the chromophore or chromophores ...Continue Reading

References

Nov 24, 2004·Protein Science : a Publication of the Protein Society·Janka MátraiYves Engelborghs

Related Concepts

Thermodynamics
Derivatives
Histidine
Methane
Sulfoxides
Methylate
Ions
Alpha-chymotrypsin
Oxidation
Avazyme

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