9PCL
Crystal structure of Rv0097 with 10 mM CADA soaked (CADA bound)
Summary for 9PCL
| Entry DOI | 10.2210/pdb9pcl/pdb |
| Descriptor | (3R)-3-[(carboxymethyl)amino]fatty acid oxygenase/decarboxylase, (3R)-3-(2-hydroxy-2-oxoethylamino)decanoic acid, FE (III) ION, ... (5 entities in total) |
| Functional Keywords | non-heme iron enzyme, fe(ii)/alpha-ketoglutarate-dependent dioxygenases, isonitrile synthase, oxidoreductase |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 4 |
| Total formula weight | 138019.50 |
| Authors | |
| Primary citation | Ye, N.,Del Rio Flores, A.,Zhang, W.,Drennan, C.L. A highly dynamic mononuclear non-heme iron enzyme for the two-step isonitrile biosynthesis. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: The recent discovery of the isonitrile biosynthetic enzyme ScoE expanded the catalytic repertoire of the Fe(II)/αKG-dependent dioxygenase enzyme family. ScoE synthesizes an isonitrile functional group from a glycyl-fatty acid adduct, with both the isonitrile nitrogen and carbon atoms coming from the glycyl moiety. This challenging chemistry cannot be performed in a single step. Instead, the mechanism appears to require two half reactions, each involving αKG cleavage to generate a highly reactive iron-oxygen species. Here, we report sixteen crystal structures that provide snapshots along the reaction trajectory of Rv0097, a ScoE homolog from Mycobacterium tuberculosis. These structures, which are both of wild-type and Rv0097 variants, include a substrate 3-((carboxymethyl)amino)decanoic acid (CADA)-bound structure, an αKG-bound structure, and a structure with both CADA and αKG bound. These structural data reveal how Rv0097 employs conformational rearrangements to protect the unstable CADA-reaction intermediate that is formed in the first half reaction while swapping out αKG cleavage products for a second molecule of αKG. Additionally, these structures, together with data from site-directed mutagenesis, provide insight into Rv0097's preference for substrates with long alkyl chains, potentially facilitating efforts to re-engineer ScoE/Rv0097 to synthesize isonitrile functional groups on a wider range of small molecules. PubMed: 41587996DOI: 10.1038/s41467-026-68588-w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.76 Å) |
Structure validation
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