6RMD

Structure of ATP bound Plasmodium falciparum IMP-nucleotidase

Summary for 6RMD

• Entry DOI: 10.2210/pdb6rmd/pdb
• Related: 6RME 6RMO 6RMW 6RN1 6RNH
• Descriptor: IMP-specific 5'-nucleotidase, putative, 1,2-ETHANEDIOL, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: nucleotidase, hydrolase, activator, complex, biosynthetic protein
• Biological source: Plasmodium falciparum (isolate 3D7); More
• Total number of polymer chains: 2
• Total formula weight: 94988.84

Authors

Carrique, L.,Ballut, L.,Violot, S.,Aghajari, N. (deposition date: 2019-05-06, release date: 2020-07-15, Last modification date: 2024-05-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)