ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P38. Structural Models of LADH Active Site. Pentacoordination of
Catalytic Zinc Derived from Model Studies
A. Dołęga a , K. Baranowska a , A. Herman a , D. Gudat b
a
Gdańsk University of Technology,Department of Inorganic Chemistry,Narutowicza St. 11/12, 80-952, Gdańsk,
Poland
e-mail: ania@chem.pg.gda.pl.
b
Institut für Anorganische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Zinc in horse liver alcohol dehydrogenase (EC 1.1.1.1, LADH) supports a reversible oxidation of alcohols to
aldehydes [1]. The detailed mechanism of the action of LADH is still under discussion. The coordination
environment of the zinc ion located in the active site is an example of an unsolved problem. The geometry of the
ligands is usually described as pseudotetrahedral [1], but there are also data, which point to the presence of five
ligands in the first coordination sphere [2].
Close structural models of the LADH active site have been obtained and characterized by FT-IR, NMR and Xray
diffraction. It has been shown that, similar to a manganese complex [3], zinc and cadmium tri-tertbutoxysilanethiolates
with 2-methylimidazole as a co-ligand are able to bind alcohol. Comparison of the
geometry of model complexes with the crystal data for ADH proteins indicates five-coordinated catalytic zinc
ion in LADH. Our studies support the idea of Ryde [4], that glu68 participates in the reaction catalyzed by
LADH as a fifth ligand to zinc.
Both geometrical and electronic features of the active site ligands are reproduced in the presented models. The
113 Cd NMR shift of one of the cadmium silanethiolates is identical with the shift of a Cd-substituted LADH-
NAD + complex [5,6] on a 1000 ppm scale of 113 Cd NMR shifts.
Quantum mechanical calculations with the zinc complex 1 as a starting model show a 20% decrease in the
enthalpy of ethanol deprotonation due to complexation with Zn 2+ .
Acknowledgement: The financial support of Polish Ministry of Science and Higher Education - Grant No. N
N204 274835 - is acknowledged.
References:
[1] G. Parkin, Chem. Rev., 104, 699 (2004).
[2] R. Meijers, R. J. Morris, H. W. Adolph, A. Merli, V. S. Lamzin, E. S. Cedergren-Zeppezauer, J.Biol.Chem.,
276, 9316 (2001).
[3] A. Kropidłowska, J. Chojnacki, B. Becker, J. Inorg. Biochem., 101, 578 (2007).
[4] U.Ryde, Protein Sci., 4, 1124 (1995).
[5] B.R. Bobsein, R.J. Myers, J. Biol. Chem., 256, 5313 (1981).
[6] A. Dołęga, K. Baranowska, J. Gajda, S. Kaźmierski, M. Potrzebowski, Inorg. Chim. Acta, 360, 2973 (2007).
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