8RY6
CryoEM structure of M. smegmatis GMP reductase apoform at pH 6.6, extended conformation I.
Summary for 8RY6
| Entry DOI | 10.2210/pdb8ry6/pdb |
| Related | 8RY5 |
| EMDB information | 19588 |
| Descriptor | GMP reductase (1 entity in total) |
| Functional Keywords | gmp reductase, guab1, cbs domain, mycobacterium smegmatis, oxidoreductase |
| Biological source | Mycolicibacterium smegmatis |
| Total number of polymer chains | 8 |
| Total formula weight | 414259.47 |
| Authors | Dolezal, M.,Kouba, T.,Pichova, I. (deposition date: 2024-02-08, release date: 2025-08-20, Last modification date: 2026-04-22) |
| Primary citation | Dolezal, M.,Knejzlik, Z.,Kouba, T.,Filimonenko, A.,Svachova, H.,Dedola, M.,Klima, M.,Pichova, I. Structural basis for allosteric regulation of mycobacterial guanosine 5 ́-monophosphate reductase by ATP and GTP. Nat Commun, 2026 Cited by PubMed Abstract: Guanosine 5'-monophosphate reductase (GMPR) is a crucial enzyme in the purine salvage pathway that catalyses the NADPH-dependent conversion of GMP to IMP, thereby contributing to purine nucleotide homeostasis. Mycobacterium smegmatis GMPR (MsmGMPR) contains a regulatory cystathionine β-synthase (CBS) domain, which mediates allosteric modulation by ATP and GTP. However, MsmGMPR exhibits an atypical tertiary structure that is incompatible with the acknowledged regulatory mechanisms of IMPDH/GMPR family enzymes. Here, we combine X-ray crystallography, cryogenic electron microscopy, and biochemical binding assays to elucidate the molecular basis of MsmGMPR regulation by ATP and GTP. We show that ATP stabilises a compressed conformation that inhibits the enzyme by restricting access to the active site and preventing NADPH binding. In contrast, GTP counteracts ATP binding, promoting an active conformation that enables catalysis. Our results provide insight into how MsmGMPR senses and responds to the purine nucleotide balance, revealing a distinct utilisation of the CBS domain compared with its typical role in IMPDH/GMPR enzymes. PubMed: 41974687DOI: 10.1038/s41467-026-71657-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.22 Å) |
Structure validation
Download full validation report
