Deciphering the nucleotide driven kinetic and oligomeric dynamics in IMPDH regulation
Ayoub, N.; Raynal, B.; Gelin, M.; Labesse, G.; Haouz, A.; Munier-Lehmann, H.
Show abstract
Inosine monophosphate dehydrogenase (IMPDH) controls guanine nucleotide biosynthesis. Here, using biochemical and integrative structural biology approaches, we characterize the class II bacterial IMPDH from Burkholderia thailandensis. We demonstrate that MgGTP acts as a direct allosteric inhibitor independently of MgATP, promoting tetramer-to-octamer assembly via the Bateman domain. When both nucleotides are present, the enzyme exhibits a biphasic response: low MgGTP concentrations enhance activity, whereas higher concentrations restore inhibition. Structural analyses reveal distinct octameric conformations and capture a pre-catalytic Michaelis complex with substrates and effectors bound. These findings uncover a regulatory mechanism where the Bateman domain integrates opposing nucleotide signals to dynamically control guanine nucleotide biosynthesis, highlighting IMPDH as a potential antimicrobial target in pathogenic Burkholderia species.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Structural basis of S-adenosylmethionine-dependent Allosteric Transition from Active to Inactive States in Methylenetetrahydrofolate Reductase 97%
- Cyclodipeptide oxidase is an enzyme filament 97%
- Coordinated conformational changes in the Tad pilus ATPase CpaF facilitate a rotary mechanism of catalysis 96%
Similar papers in this journal
Similar papers in this journal
- Hybrid histidine kinase activation by cyclic di-GMP- mediated domain liberation 96%
- Structural elucidation of the heterodimeric cis-prenyltransferase NgBR/DHDDS complex reveals novel insights in regulation of protein glycosylation 96%
- Insertions and deletions mediated functional divergence of Rossmann fold enzymes 96%
Similar papers in this journal
- Differences in the regulation mechanisms of the glutamine synthetase from methanogenic archaea unveiled by structural investigations 96%
- Crystal structures reveal nucleotide-induced conformational changes in G motifs and distal regions in guanylate-binding protein 2 95%
- Cryo-EM structure of the transcription termination factor Rho from Mycobacterium tuberculosis reveals mechanism of resistance to bicyclomycin 95%
Similar papers in this journal
- Structural basis of substrate specificity of Helix pomatia AMP deaminase and a chimeric ADGF adenosine deaminase 97%
- The mechanism of peptidoglycan O-acetylation in Gram-negative bacteria typifies bacterial MBOAT-SGNH acyltransferases 96%
- Structures of a lipin/Pah phosphatidic acid phosphatase in distinct catalytic states reveal a signature motif for substrate recognition 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.