Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00618752" target="_blank" >RIV/61388963:_____/25:00618752 - isvavai.cz</a>
Alternative codes found
RIV/00216224:90127/25:00143918
Result on the web
<a href="https://doi.org/10.1016/j.jsb.2025.108198" target="_blank" >https://doi.org/10.1016/j.jsb.2025.108198</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jsb.2025.108198" target="_blank" >10.1016/j.jsb.2025.108198</a>

Result language
angličtina
Original language name
Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface
Original language description
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 barrellike 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 IMPDHtargeted drugs.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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