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Kinetic mechanism of the interaction of D-cycloserine with serine hydroxymethyltransferase.

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Title Kinetic mechanism of the interaction of D-cycloserine with serine hydroxymethyltransferase.
 
Creator Manohar, R.
Appu Rao, A. G.
Appaji Rao, N.
 
Subject 07 Enzyme Biochemistry
 
Description The kinetic mechanism for the interaction of
D-cycloserine with serine hydroxymethyltransferase (EC
2.1.2.1) from sheep liver was established by measuring changes
in the activity, absorbance, and circular dichoism (CD) of the
enzyme. The irreversible inhibition of the enzyme was
characterized by three detectable steps: an initial rapid step
followed by two successive steps with rate constants of 5.4 X
s-l and 1.4 X lo4 s-l. The first step was distinguished
by a rapid disappearance of the enzyme absorbance peak at
425 nm, a decrease in the enzyme activity to 25% of the
uninhibited velocity, and a lowering of the CD intensity at 432
nm to about 65% of the original value. The second step of
the interaction was accompanied by a complete loss of enzyme activity and a marginal increase in the CD intensity at 432
nm. The final step resulted in the complete loss of the enzyme
absorbance at 425 nm and of the CD band at 432 nm. The
products of the reaction were identified as (a) apoenzyme by
absorbance measurements, CD spectra, and reconstitution with
pyridoxal 5’-phosphate and (b) a pyridoxal 5’-phosphate-~-
cycloserine Schiff s base complex identified by its fluorescence
and absorbance spectra. The Schiff base complex was expelled
from the enzyme active site in the final step of the reaction.
The proposed mechanism, which is different from those operative
in other pyridoxal phosphate dependent enzymes,
probably accounts for the selective inhibition of serine hydroxymethyltransferase
by the drug in vivo.
 
Date 1984
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/4532/1/Biochemistry%201984%2C%2023%2C%2041%2016-4122.pdf
Manohar, R. and Appu Rao, A. G. and Appaji Rao, N. (1984) Kinetic mechanism of the interaction of D-cycloserine with serine hydroxymethyltransferase. Biochemistry, 23. pp. 4116-4122.