4WZH

Dihydroorotate dehydrogenase from Leishmania Viannia braziliensis

4WZH の概要

• エントリーDOI: 10.2210/pdb4wzh/pdb
• 関連するPDBエントリー: 3GYE
• 分子名称: Dihydroorotate dehydrogenase, FLAVIN MONONUCLEOTIDE, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: dihydroorotate dehydrogenase, oxidoreductase
• 由来する生物種: Leishmania braziliensis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76046.66

構造登録者

Reis, R.A.G.,Lorenzato, E.,Silva, V.C.,Nonato, M.C. (登録日: 2014-11-19, 公開日: 2015-05-13, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.12 Å)