Stereochemical constraint in the evolution of pyridoxal-5'-phosphate-dependent enzymes. A hypothesis

FEBS Letters
P ChristenM Sterk

Abstract

In the transamination reactions undergone by pyridoxal-5'-phosphate-dependent enzymes that act on L-amino acids, the C4' atom of the cofactor is without exception protonated from the si side. This invariant absolute stereochemistry of enzymes not all of which are evolutionarily related to each other and the inverse stereochemistry in the case of D-alanine aminotransferase might reflect a stereochemical constraint in the evolution of these enzymes rather than an accidental historical trait passed on from a common ancestor enzyme. Conceivably, the coenzyme and substrate binding sites of primordial pyridoxal-5'-phosphate-dependent enzymes had to fulfil the following prerequisites in order to allow their development toward effective catalysts: (i) the negatively charged alpha-carboxylate group of the amino acid substrate had to be positioned as far as possible away from the negatively charged phosphate group of the cofactor, and (ii) the C alpha-H bond had to be oriented toward the protein. Compliance with these two criteria implies, under the assumption that C4' is protonated by an acid-base group of the protein, the observed stereochemical feature.

References

May 20, 1992·Journal of Molecular Biology·C A McPhalenJ N Jansonius
Dec 16, 1974·European Journal of Biochemistry·V G TumanyanG I Yakovlev
Oct 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·H C Dunathan, J G Voet
Apr 1, 1966·Proceedings of the National Academy of Sciences of the United States of America·H C Dunathan
Apr 15, 1984·Journal of Molecular Biology·J F KirschP Christen
Apr 27, 1993·Biochemistry·A A AntsonK S Wilson
May 1, 1994·European Journal of Biochemistry·E SandmeierP Christen

Citations

Jul 9, 1999·Journal of Molecular Recognition : JMR·A HuberD Neri
Apr 5, 2002·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·P Christen, P K Mehta
Oct 16, 2002·Journal of Immunological Methods·S I GramatikovaP Christen
Jun 23, 2006·The Journal of Biological Chemistry·Béatrice Golinelli-PimpaneauP Christen

Related Concepts

Pyridoxal Phosphate
Molecular Stereochemistry
Substrate Specificity
Evolution, Molecular

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