8SWU

Structure of Clostridium perfringens PNP bound to transition state analog IMMUCILLIN H and sulfate

8SWU の概要

• エントリーDOI: 10.2210/pdb8swu/pdb
• 分子名称: Purine nucleoside phosphorylase, 1,4-DIDEOXY-4-AZA-1-(S)-(9-DEAZAHYPOXANTHIN-9-YL)-D-RIBITOL, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: pentosyltransferase, purine nucleoside phosphorylase, transferase
• 由来する生物種: Clostridium perfringens ATCC 13124
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 90493.72

構造登録者

Fedorov, E.,Ghosh, A. (登録日: 2023-05-19, 公開日: 2023-10-18, 最終更新日: 2023-11-22)

主引用文献

Minnow, Y.V.T.,Schramm, V.L.,Almo, S.C.,Ghosh, A.
Phosphate Binding in PNP Alters Transition-State Analogue Affinity and Subunit Cooperativity.
Biochemistry, 62:3116-3125, 2023

PubMed Abstract: Purine nucleoside phosphorylases (PNPs) catalyze the phosphorolysis of 6-oxypurine nucleosides with an HPO dianion nucleophile. Nucleosides and phosphate occupy distinct pockets in the PNP active site. Evaluation of the HPO site by mutagenesis, cooperative binding studies, and thermodynamic and structural analysis demonstrate that alterations in the HPO binding site can render PNP inactive and significantly impact subunit cooperativity and binding to transition-state analogue inhibitors. Cooperative interactions between the cationic transition-state analogue and the anionic HPO nucleophile demonstrate the importance of reforming the transition-state ensemble for optimal inhibition with transition-state analogues. Altered phosphate binding in the catalytic site mutants helps to explain one of the known lethal PNP deficiency syndromes in humans.

PubMed: 37812583
DOI: 10.1021/acs.biochem.3c00264

実験手法

X-RAY DIFFRACTION (2.34 Å)