9I0L

Mycobacterium smegmatis inosine monophosphate dehydrogenase (IMPDH) E-XMP* intermediate, extended

Summary for 9I0L

• Entry DOI: 10.2210/pdb9i0l/pdb
• Related: 9I0K
• EMDB information: 52560
• Descriptor: Inosine-5'-monophosphate dehydrogenase, INOSINIC ACID, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: octamer, reaction intermediate, purine metabolism, impdh, oxidoreductase
• Biological source: Mycolicibacterium smegmatis MC2 155
• Total number of polymer chains: 8
• Total formula weight: 435517.74

Authors

Bulvas, O.,Kouba, T.,Pichova, I. (deposition date: 2025-01-15, release date: 2025-03-26, Last modification date: 2025-04-02)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.39 Å)