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

J 2025

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

BULVAS, Ondrej; Zdenek KNEJZLIK; Anatolij FILIMONENKO; Tomas KOUBA; Iva PICHOVA et al.

Základní údaje

Originální název

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

Autoři

BULVAS, Ondrej; Zdenek KNEJZLIK; Anatolij FILIMONENKO; Tomas KOUBA a Iva PICHOVA

Vydání

Journal of Structural Biology, UNITED STATES, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2025, 1047-8477

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10400 1.4 Chemical sciences

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.700 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:90127/25:00143918

Organizační jednotka

CIISB II

Klíčová slova anglicky

IMPDH; Octamerization; Cryo-EM; Conformational dynamics; Mycobacterium

Štítky

CF CRYO, ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 3. 2026 10:21, Mgr. Eva Dubská

Anotace

V originále

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.

Návaznosti

90242, velká výzkumná infrastruktura

Název: CIISB III

Citovat

BULVAS, Ondrej; Zdenek KNEJZLIK; Anatolij FILIMONENKO; Tomas KOUBA a Iva PICHOVA. Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface. Journal of Structural Biology. UNITED STATES: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2025, roč. 217, č. 2, s. 1-9. ISSN 1047-8477. Dostupné z: https://doi.org/10.1016/j.jsb.2025.108198.

@article{2559437,
   author = {Bulvas, Ondrej and Knejzlik, Zdenek and Filimonenko, Anatolij and Kouba, Tomas and Pichova, Iva},
   article_location = {UNITED STATES},
   article_number = {2},
   doi = {https://doi.org/10.1016/j.jsb.2025.108198},
   keywords = {IMPDH; Octamerization; Cryo-EM; Conformational dynamics; Mycobacterium},
   language = {eng},
   issn = {1047-8477},
   journal = {Journal of Structural Biology},
   title = {Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface},
   url = {https://pdf.sciencedirectassets.com/272607/1-s2.0-S1047847725X00022/1-s2.0-S1047847725000334/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEHoaCXVzLWVhc3QtMSJHMEUCIDCTX9YIBP3RJdmhVULk24ZcJ55q%2Fm676KVICTjGVRP3AiEAwFHhfel9z%2B%2BVUfUPVilETWjcyzUwKCOLP%2Bj},
   volume = {217},
   year = {2025}
}

TY  - JOUR
ID  - 2559437
AU  - Bulvas, Ondrej - Knejzlik, Zdenek - Filimonenko, Anatolij - Kouba, Tomas - Pichova, Iva
PY  - 2025
TI  - Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface
JF  - Journal of Structural Biology
VL  - 217
IS  - 2
SP  - 1-9
EP  - 1-9
PB  - ACADEMIC PRESS INC ELSEVIER SCIENCE
SN  - 10478477
KW  - IMPDH
KW  - Octamerization
KW  - Cryo-EM
KW  - Conformational dynamics
KW  - Mycobacterium
UR  - https://pdf.sciencedirectassets.com/272607/1-s2.0-S1047847725X00022/1-s2.0-S1047847725000334/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEHoaCXVzLWVhc3QtMSJHMEUCIDCTX9YIBP3RJdmhVULk24ZcJ55q%2Fm676KVICTjGVRP3AiEAwFHhfel9z%2B%2BVUfUPVilETWjcyzUwKCOLP%2Bj
N2  - 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.
ER  -

BULVAS, Ondrej; Zdenek KNEJZLIK; Anatolij FILIMONENKO; Tomas KOUBA a Iva PICHOVA. Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface. \textit{Journal of Structural Biology}. UNITED STATES: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2025, roč.~217, č.~2, s.~1-9. ISSN~1047-8477. Dostupné z: https://doi.org/10.1016/j.jsb.2025.108198.

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