4WZH

Dihydroorotate dehydrogenase from Leishmania Viannia braziliensis

Summary for 4WZH

• Entry DOI: 10.2210/pdb4wzh/pdb
• Related: 3GYE
• Descriptor: Dihydroorotate dehydrogenase, FLAVIN MONONUCLEOTIDE, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (5 entities in total)
• Functional Keywords: dihydroorotate dehydrogenase, oxidoreductase
• Biological source: Leishmania braziliensis
• Total number of polymer chains: 2
• Total formula weight: 76046.66

Authors

Reis, R.A.G.,Lorenzato, E.,Silva, V.C.,Nonato, M.C. (deposition date: 2014-11-19, release date: 2015-05-13, Last modification date: 2023-09-27)

Primary citation

Reis, R.A.,Lorenzato, E.,Silva, V.C.,Nonato, M.C.
Recombinant production, crystallization and crystal structure determination of dihydroorotate dehydrogenase from Leishmania (Viannia) braziliensis.
Acta Crystallogr.,Sect.F, 71:547-552, 2015

PubMed Abstract: The enzyme dihydroorotate dehydrogenase (DHODH) is a flavoenzyme that catalyses the oxidation of dihydroorotate to orotate in the de novo pyrimidine-biosynthesis pathway. In this study, a reproducible protocol for the heterologous expression of active dihydroorotate dehydrogenase from Leishmania (Viannia) braziliensis (LbDHODH) was developed and its crystal structure was determined at 2.12 Å resolution. L. (V.) braziliensis is the species responsible for the mucosal form of leishmaniasis, a neglected disease for which no cure or effective therapy is available. Analyses of sequence, structural and kinetic features classify LbDHODH as a member of the class 1A DHODHs and reveal a very high degree of structural conservation with the previously reported structures of orthologous trypanosomatid enzymes. The relevance of nucleotide-biosynthetic pathways for cell metabolism together with structural and functional differences from the respective host enzyme suggests that inhibition of LbDHODH could be exploited for antileishmanicidal drug development. The present work provides the framework for further integrated in vitro, in silico and in vivo studies as a new tool to evaluate DHODH as a drug target against trypanosomatid-related diseases.

PubMed: 25945707
DOI: 10.1107/S2053230X15000886

Experimental method

X-RAY DIFFRACTION (2.12 Å)