MinireviewReaction specificity in pyridoxal phosphate enzymes☆
Section snippets
Model studies
The degree to which the Schiff base vs. the pyridine ring contributes to the stabilization of Cα carbanions has been debated recently. Computational studies performed by our group [5] and that of Bach [6] both predict that the pyridine ring does not play the largest role in carbanion stabilization as is commonly accepted in the literature [1], [7], [8]. Our studies used semi-empirical molecular orbital methods (PM3) to study both model aldimines and the intermediates formed in the active site
Dialkylglycine decarboxylase
This unusual and interesting PLP enzyme catalyzes the two half-reactions shown in Fig. 5A. The first is a decarboxylation reaction where 2,2-dialkylglycines lose CO2 to give a carbanion that is subsequently protonated on C4′ of the coenzyme instead of the proton replacing the CO2 on Cα of the amino acid substrate, as typical decarboxylases do. This leads to the ketone product and the PMP form of the coenzyme, as occurs in aminotransferase mechanisms. The second half-reaction is a classical
Alanine racemase
The racemization of alanine is important to bacterial survival since d-alanine is a component of the peptidoglycan layer of the cell wall structure. The X-ray structure [25], [26], [27] shows several interesting active site features. Among these are the disposition of Lys39 (which forms the Schiff base with PLP in the resting enzyme) and Tyr265 on opposite faces of the substrate Cα. This is readily seen in the structure of the complex of alanine phosphonate with alanine racemase [27], which is
References (36)
- et al.
Kinetic characterization of transient free radical intermediates in reaction of lysine 2,3-aminomutase by EPR lineshape analysis
Methods Enzymol.
(2002) Pyridoxal phosphate-dependent enzymes
Biochim. Biophys. Acta
(1995)- et al.
Quantitative description of absorption spectra of a pyridoxal phosphate-dependent enzyme using lognormal distribution curves
Anal. Biochem.
(1987) - et al.
Structural and mechanistic analysis of two refined crystal structures of the pyridoxal phosphate-dependent enzyme dialkylglycine decarboxylase
J. Mol. Biol.
(1995) - et al.
Crystal structures of dialkylglycine decarboxylase inhibitor complexes
J. Mol. Biol.
(1999) - et al.
Role of lysine 39 of alanine racemase from Bacillus stearothermophilus that binds pyridoxal 5′-phosphate - Chemical rescue studies of Lys(39) → Ala mutant
J. Biol. Chem.
(1999) Program DYNAFIT for the analysis of enzyme kinetic data: application to HIV proteinase
Anal. Biochem.
(1996)- et al.
Transaminases
(1985) - et al.
S-Adenosylmethionine: a ‘poor man’s coenzyme B12’ in the reaction of lysine 2,3-aminomutase
Biochem. Soc. Trans.
(1998) - et al.
A genomic overview of pyridoxal-phosphate-dependent enzymes
EMBO Rep.
(2003)
Computational studies on nonenzymatic and enzymatic pyridoxal phosphate catalyzed decarboxylations of 2-aminoisobutyrate
Biochemistry
Influence of electrostatic effects on activation barriers in enzymatic reactions: Pyridoxal 5′-phosphate-dependent decarboxylation of alpha-amino acids
J. Am. Chem. Soc.
Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations
Annu. Rev. Biochem.
Pyruvoyl-dependent enzymes
Annu. Rev. Biochem.
Aldolase: a model for enzyme structure–function relationships
Essays Biochem.
J. Am. Chem. Soc.
Metal ion inhibition of nonenzymatic pyridoxal phosphate catalyzed decarboxylation and transamination
J. Am. Chem. Soc.
Comparison of the rate constants for general base catalyzed prototropy and racemization of the aldimine species formed from 3-hydroxypyridine-4-carboxaldehyde and alanine
Biochemistry
Cited by (0)
- ☆
This work was supported by Grant GM54779 from the National Institutes of Health.