4RHK

Crystal structure of T. brucei arginase-like protein in an oxidized form

4RHK の概要

• エントリーDOI: 10.2210/pdb4rhk/pdb
• 関連するPDBエントリー: 4RHI 4RHJ 4RHL 4RHM 4RHQ
• 分子名称: Arginase, GLYCEROL (3 entities in total)
• 機能のキーワード: arginase/deacetylase fold, unknown function
• 由来する生物種: Trypanosoma brucei brucei
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38824.34

構造登録者

Hai, Y.,Barrett, M.P.,Christianson, D.W. (登録日: 2014-10-02, 公開日: 2014-12-31, 最終更新日: 2015-02-04)

主引用文献

Hai, Y.,Kerkhoven, E.J.,Barrett, M.P.,Christianson, D.W.
Crystal Structure of an Arginase-like Protein from Trypanosoma brucei That Evolved without a Binuclear Manganese Cluster.
Biochemistry, 54:458-471, 2015

PubMed Abstract: The X-ray crystal structure of an arginase-like protein from the parasitic protozoan Trypanosoma brucei, designated TbARG, is reported at 1.80 and 2.38 Å resolution in its reduced and oxidized forms, respectively. The oxidized form of TbARG is a disulfide-linked hexamer that retains the overall architecture of a dimer of trimers in the reduced form. Intriguingly, TbARG does not contain metal ions in its putative active site, and amino acid sequence comparisons indicate that all but one of the residues required for coordination to the catalytically obligatory binuclear manganese cluster in other arginases are substituted here with residues incapable of metal ion coordination. Therefore, the structure of TbARG is the first of a member of the arginase/deacetylase superfamily that is not a metalloprotein. Although we show that metal binding activity is easily reconstituted in TbARG by site-directed mutagenesis and confirmed in X-ray crystal structures, it is curious that this protein and its parasitic orthologues evolved away from metal binding function. Knockout of the TbARG gene from the genome demonstrated that its function is not essential to cultured bloodstream-form T. brucei, and metabolomics analysis confirmed that the enzyme has no role in the conversion of l-arginine to l-ornithine in these cells. While the molecular function of TbARG remains enigmatic, the fact that the T. brucei genome encodes only this protein and not a functional arginase indicates that the parasite must import l-ornithine from its host to provide a source of substrate for ornithine decarboxylase in the polyamine biosynthetic pathway, an active target for the development of antiparasitic drugs.

PubMed: 25536859
DOI: 10.1021/bi501366a

実験手法

X-RAY DIFFRACTION (2.38 Å)