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Gene Review

kynU  -  kynureninase

Pseudomonas protegens Pf-5

 
 
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Disease relevance of kynU

  • Three-dimensional structure of kynureninase from Pseudomonas fluorescens [1].
  • The resultant plasmid was used to transform E. coli DH5alpha F', and these cells overexpressed kynureninase to about 37% of total soluble protein [2].
 

High impact information on kynU

  • Beta-benzoyl-L-alanine is a good substrate of kynureninase from Pseudomonas fluorescens, with k(cat) and k(cat)/K(m) values of 0.7 s(-1) and 8.0 x 10(4) M(-1) s(-1), respectively, compared to k(cat) = 16.0 s(-1) and k(cat)/K(m) = 6.0 x 10(5) M(-1) s(-1) for L-kynurenine [3].
  • Kynureninase [E.C. 3.7.1.3] is a pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes the hydrolytic cleavage of l-kynurenine to anthranilic acid and l-alanine [1].
  • On the basis of these observations, we propose that the rate-limiting step in the reaction of kynureninase is C-4' deprotonation of the pyruvate pyridoxamine 5'-phosphate ketimine intermediate [4].
  • The reaction of L-alanine with kynureninase exhibits the rapid formation (386 s-1 at 0.1 M) of an external aldimine intermediate absorbing at 420 nm, followed by slower formation of a quinonoid intermediate with a peak at 500 nm (k = 2.5 s-1) [5].
  • In contrast, the reaction of kynureninase with 0.5 mM l-kynurenine in the presence of 10 mM benzaldehyde results in the formation of a quinonoid intermediate (k = 67.4 s-1) with a very strong absorbance peak at 496 nm [5].
 

Chemical compound and disease context of kynU

 

Biological context of kynU

 

Associations of kynU with chemical compounds

  • Mixing kynureninase with 0.5 mM L-kynurenine results in formation of a quinonoid intermediate, with lambdamax = 494 nm, within the dead time (ca. 2 ms) of the stopped-flow mixer [5].
  • Taken together, these data indicate that the rate-limiting step in the reaction of kynureninase occurs subsequent to the first irreversible step, which is anthranilate release, is general base catalyzed, and involves transfer of only a single proton [4].
  • Based on this alignment, we predict that Lys227 and Asp212 in P. fluorescens kynureninase are involved in pyridoxal-5'-phosphate binding [2].
  • Several kynurenine analogs have been prepared and examined for their susceptibility to hydrolytic cleavage by bacterial kynureninase [8].
  • It was shown that kynurenic acid is not produced by kynureninase by the use of isotopically labeled substrate [8].

References

  1. Three-dimensional structure of kynureninase from Pseudomonas fluorescens. Momany, C., Levdikov, V., Blagova, L., Lima, S., Phillips, R.S. Biochemistry (2004) [Pubmed]
  2. Cloning, sequence, and expression of kynureninase from Pseudomonas fluorescens. Koushik, S.V., Sundararaju, B., McGraw, R.A., Phillips, R.S. Arch. Biochem. Biophys. (1997) [Pubmed]
  3. Reaction of Pseudomonas fluorescens kynureninase with beta-benzoyl-L-alanine: detection of a new reaction intermediate and a change in rate-determining step. Gawandi, V.B., Liskey, D., Lima, S., Phillips, R.S. Biochemistry (2004) [Pubmed]
  4. The catalytic mechanism of kynureninase from Pseudomonas fluorescens: insights from the effects of pH and isotopic substitution on steady-state and pre-steady-state kinetics. Koushik, S.V., Moore, J.A., Sundararaju, B., Phillips, R.S. Biochemistry (1998) [Pubmed]
  5. The catalytic mechanism of kynureninase from Pseudomonas fluorescens: evidence for transient quinonoid and ketimine intermediates from rapid-scanning stopped-flow spectrophotometry. Phillips, R.S., Sundararaju, B., Koushik, S.V. Biochemistry (1998) [Pubmed]
  6. Stereospecificity of Pseudomonas fluorescens kynureninase for diastereomers of beta-methylkynurenine. Cyr, L.V., Newton, M.G., Phillips, R.S. Bioorg. Med. Chem. (1999) [Pubmed]
  7. Kynureninase-Type enzymes of Penicillum roqueforti, Aspergillus niger, Rhizopus stolonifer, and Pseudomonas fluorescens: further evidence for distinct kynureninase and hydroxykynureninase activities. Shetty, A.S., Gaertner, F.H. J. Bacteriol. (1975) [Pubmed]
  8. The mechanism of kynurenine hydrolysis catalyzed by kynureninase. Tanizawa, K., Soda, K. J. Biochem. (1979) [Pubmed]
 
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