6WTE
Structure of radical S-adenosylmethionine methyltransferase, TsrM, from Kitasatospora setae with cobalamin and [4Fe-4S] cluster bound
Summary for 6WTE
| Entry DOI | 10.2210/pdb6wte/pdb |
| Related | 6WTF |
| Descriptor | B12-binding domain-containing protein, IRON/SULFUR CLUSTER, COBALAMIN, ... (5 entities in total) |
| Functional Keywords | radical sam, cobalamin, fes cluster, methyltransferase, transferase |
| Biological source | Kitasatospora setae |
| Total number of polymer chains | 2 |
| Total formula weight | 132754.52 |
| Authors | Knox, H.L.,Chen, P.Y.-T.,Drennan, C.L.,Booker, S.J. (deposition date: 2020-05-02, release date: 2020-12-23, Last modification date: 2024-03-06) |
| Primary citation | Knox, H.L.,Chen, P.Y.,Blaszczyk, A.J.,Mukherjee, A.,Grove, T.L.,Schwalm, E.L.,Wang, B.,Drennan, C.L.,Booker, S.J. Structural basis for non-radical catalysis by TsrM, a radical SAM methylase. Nat.Chem.Biol., 17:485-491, 2021 Cited by PubMed Abstract: Tryptophan 2C methyltransferase (TsrM) methylates C2 of the indole ring of L-tryptophan during biosynthesis of the quinaldic acid moiety of thiostrepton. TsrM is annotated as a cobalamin-dependent radical S-adenosylmethionine (SAM) methylase; however, TsrM does not reductively cleave SAM to the universal 5'-deoxyadenosyl 5'-radical intermediate, a hallmark of radical SAM (RS) enzymes. Herein, we report structures of TsrM from Kitasatospora setae, which are the first structures of a cobalamin-dependent radical SAM methylase. Unexpectedly, the structures show an essential arginine residue that resides in the proximal coordination sphere of the cobalamin cofactor, and a [4Fe-4S] cluster that is ligated by a glutamyl residue and three cysteines in a canonical CXXXCXXC RS motif. Structures in the presence of substrates suggest a substrate-assisted mechanism of catalysis, wherein the carboxylate group of SAM serves as a general base to deprotonate N1 of the tryptophan substrate, facilitating the formation of a C2 carbanion. PubMed: 33462497DOI: 10.1038/s41589-020-00717-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.67 Å) |
Structure validation
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