Analysis of the wild-type and mutant genes encoding the enzyme kynurenine monooxygenase of the yellow fever mosquito, Aedes aegypti

Insect Mol Biol. 2003 Oct;12(5):483-90. doi: 10.1046/j.1365-2583.2003.00433.x.

Abstract

Kynurenine 3-monooxygenase (KMO) catalyses the hydroxylation of kynurenine to 3-hydroxykynurenine. KMO has a key role in tryptophan catabolism and synthesis of ommochrome pigments in mosquitoes. The gene encoding this enzyme in the yellow fever mosquito, Aedes aegypti, is called kynurenine hydroxylase (kh) and a mutant allele that produces white eyes has been designated khw. A number of cDNA clones representative of wild-type and mutant genes were isolated. Sequence analyses of the wild-type and mutant cDNAs revealed a deletion of 162 nucleotides in the mutant gene near the 3'-end of the deduced coding region. RT-PCR analyses confirm the transcription of a truncated mRNA in the mutant strain. The in-frame deletion results in a loss of 54 amino acids, which disrupts a major alpha-helix and which probably accounts for the loss of activity of the enzyme. Recombinant Ae. aegypti KMO showed high substrate specificity for kynurenine with optimum activity at 40 degrees C and pH = 7.5. Kinetic parameters and inhibition of KMO activity by Cl- and pyridoxal-5-phosphate were determined.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aedes / enzymology*
  • Aedes / genetics*
  • Animals
  • DNA, Complementary / genetics*
  • DNA, Complementary / isolation & purification
  • Electrophoresis, Polyacrylamide Gel
  • Gene Deletion*
  • Gene Expression Profiling
  • Kinetics
  • Kynurenine 3-Monooxygenase
  • Mixed Function Oxygenases / chemistry
  • Mixed Function Oxygenases / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment

Substances

  • DNA, Complementary
  • Mixed Function Oxygenases
  • Kynurenine 3-Monooxygenase