5X3D
Crystal structure of HEP-CMP-bound form of cytidylyltransferase (CyTase) domain of Fom1 from Streptomyces wedmorensis
Summary for 5X3D
| Entry DOI | 10.2210/pdb5x3d/pdb |
| Descriptor | Phosphoenolpyruvate phosphomutase, [[(2R,3S,4R,5R)-5-(4-azanyl-2-oxidanylidene-pyrimidin-1-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-(2-hydroxyethyl)phosphinic acid (3 entities in total) |
| Functional Keywords | cytidylyltransferase, nucleotidyltransferase, fosfomycin biosynthesis, transferase |
| Biological source | Streptomyces wedmorensis |
| Total number of polymer chains | 1 |
| Total formula weight | 18248.54 |
| Authors | Tomita, T.,Cho, S.H.,Kuzuyama, T.,Nishiyama, M. (deposition date: 2017-02-04, release date: 2017-09-13, Last modification date: 2024-03-27) |
| Primary citation | Cho, S.H.,Kim, S.Y.,Tomita, T.,Shiraishi, T.,Park, J.S.,Sato, S.,Kudo, F.,Eguchi, T.,Funa, N.,Nishiyama, M.,Kuzuyama, T. Fosfomycin Biosynthesis via Transient Cytidylylation of 2-Hydroxyethylphosphonate by the Bifunctional Fom1 Enzyme ACS Chem. Biol., 12:2209-2215, 2017 Cited by PubMed Abstract: Fosfomycin is a wide-spectrum phosphonate antibiotic that is used clinically to treat cystitis, tympanitis, etc. Its biosynthesis starts with the formation of a carbon-phosphorus bond catalyzed by the phosphoenolpyruvate phosphomutase Fom1. We identified an additional cytidylyltransferase (CyTase) domain at the Fom1 N-terminus in addition to the phosphoenolpyruvate phosphomutase domain at the Fom1 C-terminus. Here, we demonstrate that Fom1 is bifunctional and that the Fom1 CyTase domain catalyzes the cytidylylation of the 2-hydroxyethylphosphonate (HEP) intermediate to produce cytidylyl-HEP. On the basis of this new function of Fom1, we propose a revised fosfomycin biosynthetic pathway that involves the transient CMP-conjugated intermediate. The identification of a biosynthetic mechanism via such transient cytidylylation of a biosynthetic intermediate fundamentally advances the understanding of phosphonate biosynthesis in nature. The crystal structure of the cytidylyl-HEP-bound CyTase domain provides a basis for the substrate specificity and reveals unique catalytic elements not found in other members of the CyTase family. PubMed: 28727444DOI: 10.1021/acschembio.7b00419 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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