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Science 27 July 1973:
Vol. 181. no. 4097, pp. 350 - 352
DOI: 10.1126/science.181.4097.350
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Articles

Aldolase Catalysis: Single Base-Mediated Proton Activation

H. Paul Meloche 1 and Jenny Pickworth Glusker 1

1 Institute for Cancer Research, Philadelphia, Pennsylvania 19111

The enzyme, 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, catalyzes several reactions, the natural ones being (i) the exchange of hydrogen atoms of the methyl groups of pyruvate with protons of the solvent (C-H synthesis) and (ii) the reversible condensation of pyruvate with D-glyceraldehyde-3-phosphate (C-C synthesis). Previous work has provided chemical evidence for the occurrence of a protein-bound carboxylate group adjacent to the Schiff's base-forming lysine in the active site geometry. This carboxylate could provide the basic group postulated to participate in proton activation catalyzed by aldolases. With the use of three-dimensional models, it is shown that simple rotation about a carbon-carbon bond of the side chain will allow the base to assume the two positions necessary for proton activation in either the C-H synthesis or the C-C synthesis catalyzed by KDPG aldolase. This single base hypothesis provides a model wherein all reagents can approach a single face of the active site and is consistent with the stereochemistry thought to occur in the aldolase reaction.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Observation of Covalent Intermediates in an Enzyme Mechanism at Atomic Resolution.
A. Heine, G. DeSantis, J. G. Luz, M. Mitchell, C.-H. Wong, and I. A. Wilson (2001)
Science 294, 369-374
   Abstract »    Full Text »    PDF »
Covalent intermediate trapped in 2-keto-3-deoxy-6- phosphogluconate (KDPG) aldolase structure at 1.95-A resolution.
J. Allard, P. Grochulski, and J. Sygusch (2001)
PNAS 98, 3679-3684
   Abstract »    Full Text »    PDF »


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