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UDP-galactopyranose mutases from Leishmania species that cause visceral and cutaneous leishmaniasis.

Abstract
Leishmaniasis is a vector-borne, neglected tropical disease caused by parasites from the genus Leishmania. Galactofuranose (Galf) is found on the cell surface of Leishmania parasites and is important for virulence. The flavoenzyme that catalyzes the isomerization of UDP-galactopyranose to UDP-Galf, UDP-galactopyranose mutase (UGM), is a validated drug target in protozoan parasites. UGMs from L. mexicana and L. infantum were recombinantly expressed, purified, and characterized. The isolated enzymes contained tightly bound flavin cofactor and were active only in the reduced form. NADPH is the preferred redox partner for both enzymes. A kcat value of 6 ± 0.4s(-1) and a Km value of 252 ± 42 μM were determined for L. infantum UGM. For L. mexicana UGM, these values were ∼4-times lower. Binding of UDP-Galp is enhanced 10-20 fold in the reduced form of the enzymes. Changes in the spectra of the reduced flavin upon interaction with the substrate are consistent with formation of a flavin-iminium ion intermediate.
AuthorsIsabel O Fonseca, Karina Kizjakina, Pablo Sobrado
JournalArchives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 538 Issue 2 Pg. 103-10 (Oct 15 2013) ISSN: 1096-0384 [Electronic] United States
PMID24012809 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Flavins
  • Recombinant Proteins
  • NADP
  • Intramolecular Transferases
  • UDP-galactopyranose mutase
Topics
  • Amino Acid Sequence
  • Cloning, Molecular
  • Flavins (metabolism)
  • Humans
  • Intramolecular Transferases (chemistry, genetics, isolation & purification, metabolism)
  • Leishmania infantum (chemistry, enzymology, genetics, pathogenicity)
  • Leishmania mexicana (chemistry, enzymology, genetics, pathogenicity)
  • Leishmaniasis, Cutaneous (parasitology)
  • Leishmaniasis, Visceral (parasitology)
  • Molecular Sequence Data
  • NADP (metabolism)
  • Oxidation-Reduction
  • Recombinant Proteins (chemistry, genetics, isolation & purification, metabolism)
  • Sequence Alignment
  • Virulence

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