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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The dihydroorotate dehydrogenases: Past and present

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Author(s):
Reis, Renata A. G. [1] ; Calil, Felipe Antunes [2] ; Feliciano, Patricia Rosa [3] ; Pinheiro, Matheus Pinto [4] ; Nonato, M. Cristina [2]
Total Authors: 5
Affiliation:
[1] Georgia State Univ, Dept Chem, Atlanta, GA 30302 - USA
[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Lab Cristalog Prot, BR-14040903 Ribeirao Preto - Brazil
[3] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 - USA
[4] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 4
Document type: Review article
Source: Archives of Biochemistry and Biophysics; v. 632, n. SI, p. 175-191, OCT 15 2017.
Web of Science Citations: 16
Abstract

The flavoenzyme dihydroorotate dehydrogenase catalyzes the stereoselective oxidation of (S)-dihydroorotate to orotate in the fourth of the six conserved enzymatic reactions involved in the de novo pyrimidine biosynthetic pathway. Inhibition of pyrimidine metabolism by selectively targeting DHODHs has been exploited in the development of new therapies against cancer, immunological disorders, bacterial and viral infections, and parasitic diseases. Through a chronological narrative, this review summarizes the efforts of the scientific community to achieve our current understanding of structural and biochemical properties of DHODHs. It also attempts to describe the latest advances in medicinal chemistry for therapeutic development based on the selective inhibition of DHODH, including an overview of the experimental techniques used for ligand screening during the process of drug discovery. (C) 2017 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 07/08703-0 - Design of inhibitors for dihydroorotate dehydrogenase from Trypanosoma cruzi and Leishmania major
Grantee:Matheus Pinto Pinheiro
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 12/25075-0 - Development of leishmanicidal drugs based on the selective inhibition of the enzyme dihydroorotate dehydrogenase
Grantee:Maria Cristina Nonato
Support type: Regular Research Grants
FAPESP's process: 11/23504-9 - Exploring structure-function relationship of DHODH enzyme in the development of new molecules with trypanocidal and leishmanicidal activities
Grantee:Renata Almeida Garcia Reis
Support type: Scholarships in Brazil - Doctorate