9I0M

Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) saturating ATP+IMP-bound form, extended

9I0M の概要

• エントリーDOI: 10.2210/pdb9i0m/pdb
• 関連するPDBエントリー: 9I0K
• EMDBエントリー: 52561
• 分子名称: Inosine-5'-monophosphate dehydrogenase, INOSINIC ACID, POTASSIUM ION (3 entities in total)
• 機能のキーワード: octamer, ligand complex, purine metabolism, impdh, oxidoreductase
• 由来する生物種: Mycolicibacterium smegmatis MC2 155
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 430210.34

構造登録者

Bulvas, O.,Kouba, T.,Pichova, I. (登録日: 2025-01-15, 公開日: 2025-03-26, 最終更新日: 2025-04-02)

主引用文献

Bulvas, O.,Knejzlik, Z.,Filimonenko, A.,Kouba, T.,Pichova, I.
Conformational landscape of the mycobacterial inosine 5'-monophosphate dehydrogenase octamerization interface.
J.Struct.Biol., 217:108198-108198, 2025

PubMed Abstract: Inosine 5'-monophosphate dehydrogenase (IMPDH), a key enzyme in bacterial purine metabolism, plays an essential role in the biosynthesis of guanine nucleotides and shows promise as a target for antimicrobial drug development. Despite its significance, the conformational dynamics and substrate-induced structural changes in bacterial IMPDH remain poorly understood, particularly with respect to its octameric assembly. Using cryo-EM, we present full-length structures of IMPDH from Mycobacterium smegmatis (MsmIMPDH) captured in a reaction intermediate state, revealing conformational changes upon substrate binding. The structures feature resolved flexible loops that coordinate the binding of the substrate, the cofactor, and the K ion. Our structural analysis identifies a novel octamerization interface unique to MsmIMPDH. Additionally, a previously unobserved barrel-like density suggests potential self-interactions within the C-terminal regions, hinting at a regulatory mechanism tied to assembly and function of the enzyme. These data provide insights into substrate-induced conformational dynamics and novel interaction interfaces in MsmIMPDH, potentially informing the development of IMPDH-targeted drugs.

PubMed: 40107326
DOI: 10.1016/j.jsb.2025.108198

実験手法

ELECTRON MICROSCOPY (3.01 Å)