J. Hong et al., TRANSITION-STATE THEORETICAL INTERPRETATION OF THE CATALYTIC POWER OFPYRUVATE DECARBOXYLASES - THE ROLES OF STATIC AND DYNAMICAL CONSIDERATIONS, Biochimica et biophysica acta. Protein structure and molecular enzymology, 1385(2), 1998, pp. 187-200
The catalytic power of two thiamin diphosphate (ThDP)-dependent enzyme
s, yeast pyruvate decarboxylase (the hysteretically regulated enzyme f
rom Saccharomyces cerevisiae, SCPDC) and bacterial pyruvate decarboxyl
ase (the unregulated enzyme from Zymomonas mobilis, ZMPDC), are analyz
ed by thorough-going application of transition-state theory, i.e. by a
static approach that emphasizes the state-function character of the f
ree energy of activation and takes no explicit account of dynamical co
nsiderations. The overall catalytic reaction is resolved into manifold
s for addition (conversion of free enzyme and substrate to the complex
of enzyme with the pyruvate:ThDP adduct), decarboxylation, and elimin
ation (conversion of the complex of enzyme with the acetaldehyde:ThDP
adduct formed by decarboxylation into free product and free enzyme). F
or SCPDC, the addition manifold is most strongly catalyzed (3 x 10(12)
-fold, corresponding to net transition-state stabilization of 72 kJ/mo
l, transition-state stabilization of 83 kJ/mol diminished by reactant-
state stabilization of 11 kJ/mol), the decarboxylation manifold is lea
st strongly catalyzed (5x10(7)-fold, corresponding to net transition-s
tate stabilization of 41 kJ/mol, transition-state stabilization of 68
kJ/mol diminished by reactant-state stabilization of 27 kJ/mol), and t
he elimination manifold is catalyzed to an intermediate degree (2 x 10
(10)-fold, corresponding to net transition-state stabilization of 59 k
J/mol, transition-state stabilization of 76 kJ/mol diminished by react
ant-state stabilization of 17 kJ/mol). A similar situation holds for Z
MPDC, There is Ilo need to make an explicit analysis of dynamical fact
ors in order to describe the catalytic mechanism and catalytic power o
f these complex enzymes. (C) 1998 Elsevier Science B.V. All rights res
erved.