6RMW

Structure of N-terminal truncated IMP bound Plasmodium falciparum IMP-nucleotidase

6RMW の概要

• エントリーDOI: 10.2210/pdb6rmw/pdb
• 関連するPDBエントリー: 6RMD 6RME 6RMO 6RN1 6RNH
• 分子名称: IMP-specific 5'-nucleotidase, putative, INOSINIC ACID, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: nucleotidase, hydrolase, activator, complex
• 由来する生物種: Plasmodium falciparum 3D7
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 391138.93

構造登録者

Carrique, L.,Ballut, L.,Violot, S.,Aghajari, N. (登録日: 2019-05-07, 公開日: 2020-07-15, 最終更新日: 2024-01-24)

主引用文献

Carrique, L.,Ballut, L.,Shukla, A.,Varma, N.,Ravi, R.,Violot, S.,Srinivasan, B.,Ganeshappa, U.T.,Kulkarni, S.,Balaram, H.,Aghajari, N.
Structure and catalytic regulation of Plasmodium falciparum IMP specific nucleotidase.
Nat Commun, 11:3228-3228, 2020

PubMed Abstract: Plasmodium falciparum (Pf) relies solely on the salvage pathway for its purine nucleotide requirements, making this pathway indispensable to the parasite. Purine nucleotide levels are regulated by anabolic processes and by nucleotidases that hydrolyse these metabolites into nucleosides. Certain apicomplexan parasites, including Pf, have an IMP-specific-nucleotidase 1 (ISN1). Here we show, by comprehensive substrate screening, that PfISN1 catalyzes the dephosphorylation of inosine monophosphate (IMP) and is allosterically activated by ATP. Crystal structures of tetrameric PfISN1 reveal complex rearrangements of domain organization tightly associated with catalysis. Immunofluorescence microscopy and expression of GFP-fused protein indicate cytosolic localization of PfISN1 and expression in asexual and gametocyte stages of the parasite. With earlier evidence on isn1 upregulation in female gametocytes, the structures reported in this study may contribute to initiate the design for possible transmission-blocking agents.

PubMed: 32591529
DOI: 10.1038/s41467-020-17013-x

実験手法

X-RAY DIFFRACTION (3.5 Å)