2BNM
The structure of Hydroxypropylphosphonic acid epoxidase from S. wedmorenis.
Summary for 2BNM
| Entry DOI | 10.2210/pdb2bnm/pdb |
| Related | 1ZZ6 1ZZ7 1ZZ8 1ZZ9 1ZZB 1ZZC 2BNN 2BNO |
| Descriptor | EPOXIDASE, ZINC ION, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | oxidoreductase, epoxidase, cupin, hth, cation-dependant, zinc, fosfomycin |
| Biological source | STREPTOMYCES WEDMORENSIS |
| Total number of polymer chains | 2 |
| Total formula weight | 44294.02 |
| Authors | McLuskey, K.,Cameron, S.,Hunter, W.N. (deposition date: 2005-03-29, release date: 2005-10-05, Last modification date: 2011-07-13) |
| Primary citation | Mcluskey, K.,Cameron, S.,Hammerschmidt, F.,Hunter, W.N. Structure and Reactivity of Hydroxypropylphosphonic Acid Epoxidase in Fosfomycin Biosynthesis by a Cation- and Flavin-Dependent Mechanism. Proc.Natl.Acad.Sci.USA, 102:14221-, 2005 Cited by PubMed Abstract: The biosynthesis of fosfomycin, an oxirane antibiotic in clinical use, involves a unique epoxidation catalyzed by (S)-2-hydroxypropylphosphonic acid epoxidase (HPPE). The reaction is essentially dehydrogenation of a secondary alcohol. A high-resolution crystallographic analysis reveals that the HPPE subunit displays a two-domain combination. The C-terminal or catalytic domain has the cupin fold that binds a divalent cation, whereas the N-terminal domain carries a helix-turn-helix motif with putative DNA-binding helices positioned 34 A apart. The structure of HPPE serves as a model for numerous proteins, of ill-defined function, predicted to be transcription factors but carrying a cupin domain at the C terminus. Structure-reactivity analyses reveal conformational changes near the catalytic center driven by the presence or absence of ligand, that HPPE is a Zn(2+)/Fe(2+)-dependent epoxidase, proof that flavin mononucleotide is required for catalysis, and allow us to propose a simple mechanism that is compatible with previous experimental data. The participation of the redox inert Zn(2+) in the mechanism is surprising and indicates that Lewis acid properties of the metal ions are sufficient to polarize the substrate and, aided by flavin mononucleotide reduction, facilitate the epoxidation. PubMed: 16186494DOI: 10.1073/PNAS.0504314102 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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