NikJ, nikkomycin biosynthesis protein P1
Nikkomycins and polyoxins are antifungal peptidylnucleoside antibiotics active against human and plant pathogens. During peptidylnucleoside biosynthesis in Streptomyces cacaoi and S. tendae, the C5′ extension of the nucleoside essential for downstream structural diversification is catalyzed by a conserved radical S-adenosyl-L-methionine (SAM) enzyme, PolH or NikJ.
Reference Protein
- Sequence
-
Q712I6
(Sequence Homologues)
- Biological species
-
Streptomyces tendae (Bacteria)
- Cofactors
- Tetra-mu3-sulfido-tetrairon (1)
Enzyme Mechanism
Introduction
SAM is activated by the [Fe4S4]-AdoMet cluster to produce the methionine substrate and the 5'-deoxyadenosyl radical (5'-dA). The 5'-dA abstracts a hydrogen atom from the substrate, which then undergoes rearrangement to form the second ring structure. This then abstracts a hydrogen atom from Cys199 to give the final product. It is not yet clear how this residue is regenerated.
Catalytic Residues Roles
| UniProt | ||
| Cys219, Cys215, Cys222 | One of the iron-sulfur binding residues. | metal ligand |
| Cys199 | Cys199 is proposed to accept an electron from the radical activated substrate. | electron shuttle |
Chemical Components
References
- Lilla EA et al. (2016), Nat Chem Biol, 12, 905-907. Carbon extension in peptidylnucleoside biosynthesis by radical SAM enzymes. DOI:10.1038/nchembio.2187. PMID:27642865.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| Cys222 | metal ligand |
| Cys215 | metal ligand |
| Cys219 | metal ligand |
| Cys199 | electron shuttle |