8RY4

CryoEM structure of M. smegmatis GMP reductase in complex with GMP and GTP at pH 6.6, extended conformation II.

8RY4 の概要

• エントリーDOI: 10.2210/pdb8ry4/pdb
• 関連するPDBエントリー: 8RY5
• EMDBエントリー: 19586
• 分子名称: GMP reductase, GUANOSINE-5'-MONOPHOSPHATE, GUANOSINE-5'-TRIPHOSPHATE (3 entities in total)
• 機能のキーワード: gmp reductase, guab1, cbs domain, mycobacterium smegmatis, oxidoreductase
• 由来する生物種: Mycolicibacterium smegmatis
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 421350.68

構造登録者

Dolezal, M.,Kouba, T.,Pichova, I. (登録日: 2024-02-08, 公開日: 2025-08-20, 最終更新日: 2026-06-24)

主引用文献

Dolezal, M.,Knejzlik, Z.,Kouba, T.,Filimonenko, A.,Svachova, H.,Dedola, M.,Klima, M.,Pichova, I.
Structural basis for allosteric regulation of mycobacterial guanosine 5 ́-monophosphate reductase by ATP and GTP.
Nat Commun, 2026

PubMed Abstract: Guanosine 5'-monophosphate reductase (GMPR) is a crucial enzyme in the purine salvage pathway that catalyses the NADPH-dependent conversion of GMP to IMP, thereby contributing to purine nucleotide homeostasis. Mycobacterium smegmatis GMPR (MsmGMPR) contains a regulatory cystathionine β-synthase (CBS) domain, which mediates allosteric modulation by ATP and GTP. However, MsmGMPR exhibits an atypical tertiary structure that is incompatible with the acknowledged regulatory mechanisms of IMPDH/GMPR family enzymes. Here, we combine X-ray crystallography, cryogenic electron microscopy, and biochemical binding assays to elucidate the molecular basis of MsmGMPR regulation by ATP and GTP. We show that ATP stabilises a compressed conformation that inhibits the enzyme by restricting access to the active site and preventing NADPH binding. In contrast, GTP counteracts ATP binding, promoting an active conformation that enables catalysis. Our results provide insight into how MsmGMPR senses and responds to the purine nucleotide balance, revealing a distinct utilisation of the CBS domain compared with its typical role in IMPDH/GMPR enzymes.

PubMed: 41974687
DOI: 10.1038/s41467-026-71657-9

実験手法

ELECTRON MICROSCOPY (3.72 Å)