3OZF

Crystal Structure of Plasmodium falciparum Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase in complex with hypoxanthine

3OZF の概要

• エントリーDOI: 10.2210/pdb3ozf/pdb
• 関連するPDBエントリー: 3OZG
• 分子名称: Hypoxanthine-guanine-xanthine phosphoribosyltransferase, HYPOXANTHINE, PYROPHOSPHATE 2-, ... (6 entities in total)
• 機能のキーワード: hypoxanthine, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Plasmodium falciparum FCR-3/Gambia
• 細胞内の位置: Cytoplasm: P20035
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 115416.77

構造登録者

Ho, M.,Hazleton, K.Z.,Almo, S.C.,Schramm, V.L. (登録日: 2010-09-24, 公開日: 2011-09-28, 最終更新日: 2024-02-21)

主引用文献

Hazleton, K.Z.,Ho, M.C.,Cassera, M.B.,Clinch, K.,Crump, D.R.,Rosario, I.,Merino, E.F.,Almo, S.C.,Tyler, P.C.,Schramm, V.L.
Acyclic Immucillin Phosphonates: Second-Generation Inhibitors of Plasmodium falciparum Hypoxanthine- Guanine-Xanthine Phosphoribosyltransferase.
Chem.Biol., 19:721-730, 2012

PubMed Abstract: Plasmodium falciparum, the primary cause of deaths from malaria, is a purine auxotroph and relies on hypoxanthine salvage from the host purine pool. Purine starvation as an antimalarial target has been validated by inhibition of purine nucleoside phosphorylase. Hypoxanthine depletion kills Plasmodium falciparum in cell culture and in Aotus monkey infections. Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) from P. falciparum is required for hypoxanthine salvage by forming inosine 5'-monophosphate, a branchpoint for all purine nucleotide synthesis in the parasite. Here, we present a class of HGXPRT inhibitors, the acyclic immucillin phosphonates (AIPs), and cell permeable AIP prodrugs. The AIPs are simple, potent, selective, and biologically stable inhibitors. The AIP prodrugs block proliferation of cultured parasites by inhibiting the incorporation of hypoxanthine into the parasite nucleotide pool and validates HGXPRT as a target in malaria.

PubMed: 22726686
DOI: 10.1016/j.chembiol.2012.04.012

実験手法

X-RAY DIFFRACTION (1.944 Å)