Patricia R Feliciano

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Publications (2)3.53 Total impact

  • Article: Crystal structure of dihydroorotate dehydrogenase from Leishmania major.
    Artur T Cordeiro, Patricia R Feliciano, Matheus P Pinheiro, M Cristina Nonato
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    ABSTRACT: Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine biosynthetic pathway and has been exploited as the target for therapy against proliferative and parasitic diseases. In this study, we report the crystal structures of DHODH from Leishmania major, the species of Leishmania associated with zoonotic cutaneous leishmaniasis, in its apo form and in complex with orotate and fumarate molecules. Both orotate and fumarate were found to bind to the same active site and exploit similar interactions, consistent with a ping-pong mechanism described for class 1A DHODHs. Analysis of LmDHODH structures reveals that rearrangements in the conformation of the catalytic loop have direct influence on the dimeric interface. This is the first structural evidence of a relationship between the dimeric form and the catalytic mechanism. According to our analysis, the high sequence and structural similarity observed among trypanosomatid DHODH suggest that a single strategy of structure-based inhibitor design can be used to validate DHODH as a druggable target against multiple neglected tropical diseases such as Leishmaniasis, Sleeping sickness and Chagas' diseases.
    Biochimie 04/2012; 94(8):1739-48. · 3.02 Impact Factor
  • Article: Crystallization and preliminary X-ray diffraction analysis of Leishmania major dihydroorotate dehydrogenase.
    Artur T Cordeiro, Patricia R Feliciano, M Cristina Nonato
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    ABSTRACT: Dihydroorotate dehydrogenases (DHODHs) are flavin-containing enzymes that catalyze the oxidation of L-dihydroorotate to orotate, the fourth step in the de novo pyrimidine nucleotide synthesis pathway. In this study, DHODH from Leishmania major has been crystallized by the vapour-diffusion technique using lithium sulfate as the precipitating agent. The crystals belong to space group P6(1), with unit-cell parameters a = 143.7, c = 69.8 A. X-ray diffraction data were collected to 2.0 A resolution using an in-house rotating-anode generator. Analysis of the solvent content and the self-rotation function indicate the presence of two molecules in the asymmetric unit. The structure has been solved by the molecular-replacement technique.
    Acta Crystallographica Section F Structural Biology and Crystallization Communications 11/2006; 62(Pt 10):1049-51. · 0.51 Impact Factor
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