Je. Wampler et Eb. Neuhaus, A MODEL FOR THE UNUSUAL KINETICS OF THERMAL-DENATURATION OF RUBREDOXIN, Journal of protein chemistry, 16(7), 1997, pp. 721-732
The thermal denaturation of the simple, redox-active iron protein rubr
edoxin is characterized by a slow, irreversible decay of the character
istic red color of the iron center at elevated temperatures in the pre
sence of oxygen at pH 7.8. The denaturation rate is essentially consta
nt and the time period for complete bleaching is nearly independent of
protein concentration. These two characteristics of the kinetics can
be fit by a simple self-catalyzed kinetics model consisting of the com
bination of a first-order decay and catalysis by some product of that
decay, i.e., dP/dt=k(1)[A] + (k(2)[P][A])I(K-m + [Al]), where A is nat
ive rubredoxin, P, is unspecified product, k(1) is a first-order rate
constant, and k(2) and K-m are the catalytic constants. In order for t
he second term to be of this simple form over the full course of a dec
ay, the model must include the condition that the reaction is effectiv
ely irreversible. This model has properties which suggest other biolog
ical roles in regulation (changes in k(1) or k(2) can dramatically mod
ulate the kinetics), in timing (titer-independent fixed reaction time)
, and in self-activation reactions. At one extreme (k(1) much greater
than k(2)) the kinetics becomes exponential, but at the other extreme
(k(2) much greater than k(1)) they show a dramatic and rapid terminal
increase after a lag period. Some obvious possible roles in the kineti
cs of programmed cell death, prion disease, and protease autoactivatio
n are discussed.