Treponema denticola cystalysin exhibits significant alanine racemase activity accompanied by transamination: mechanistic implications

Biochem J. 2003 Apr 15;371(Pt 2):473-83. doi: 10.1042/BJ20020875.

Abstract

To obtain information on the reaction specificity of cystalysin from the spirochaete bacterium Treponema denticola, the interaction with L- and D-alanine has been investigated. Binding of both alanine enantiomers leads to the appearance of an external aldimine absorbing at 429 nm and of a band absorbing at 498 nm, indicative of a quinonoid species. Racemization and transamination reactions were observed to occur with both alanine isomers as substrates. The steady-state kinetic parameters for racemization, k (cat) and K (m), for L-alanine are 1.05+/-0.03 s(-1) and 10+/-1 mM respectively, whereas those for D-alanine are 1.4+/-0.1 s(-1) and 10+/-1 mM. During the reaction of cystalysin with L- or D-alanine, a time-dependent loss of beta-elimination activity occurs concomitantly with the conversion of the pyridoxal 5'-phosphate (PLP) coenzyme into pyridoxamine 5'-phosphate (PMP). The catalytic efficiency of the half-transamination of L-alanine is found to be 5.3x10(-5) mM(-1) x s(-1), 5-fold higher when compared with that of D-alanine. The partition ratio between racemization and half-transamination reactions is 2.3x10(3) for L-alanine and 1.4x10(4) for D-alanine. The pH dependence of the kinetic parameters for both the reactions shows that the enzyme possesses a single ionizing residue with p K values of 6.5-6.6, which must be unprotonated for catalysis. Addition of pyruvate converts the PMP form of the enzyme back into the PLP form and causes the concomitant recovery of beta-elimination activity. In contrast with other PLP enzymes studied so far, but similar to alanine racemases, the apoform of the enzyme abstracted tritium from C4' of both (4' S)- and (4' R)-[4'-(3)H]PMP in the presence of pyruvate. Together with molecular modelling of the putative binding sites of L- and D-alanine at the active site of the enzyme, the implications of these studies for the mechanisms of the side reactions catalysed by cystalysin are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / pharmacology
  • Alanine Racemase / metabolism*
  • Apoenzymes / chemistry
  • Apoenzymes / metabolism
  • Circular Dichroism
  • Cloning, Molecular
  • Cystathionine gamma-Lyase / chemistry*
  • Cystathionine gamma-Lyase / metabolism*
  • Escherichia coli / genetics
  • Kinetics
  • Models, Molecular
  • Protein Conformation
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Spectrophotometry
  • Transaminases / metabolism
  • Treponema / enzymology*

Substances

  • Apoenzymes
  • Recombinant Proteins
  • Transaminases
  • cystalysin
  • Cystathionine gamma-Lyase
  • Alanine Racemase
  • Alanine