9CH3
Structure of the alpha-N-methyltransferase (SonM) and RiPP precursor (SonA-L63D) heteromeric complex (bound to SAH)
Summary for 9CH3
| Entry DOI | 10.2210/pdb9ch3/pdb |
| Related | 7LTE 7LTF 7LTH 7LTR 7LTS 8T1S 8T1T 9CGW 9CH0 9CH1 9CH2 |
| Descriptor | TP-methylase family protein, Extradiol ring-cleavage dioxygenase LigAB LigA subunit domain-containing protein, S-ADENOSYL-L-HOMOCYSTEINE, ... (6 entities in total) |
| Functional Keywords | alpha-n-methyltransferase, transferase |
| Biological source | Shewanella oneidensis More |
| Total number of polymer chains | 8 |
| Total formula weight | 153094.22 |
| Authors | Crone, K.K.,Labonte, J.W.,Elias, M.,Freeman, M.F. (deposition date: 2024-07-01, release date: 2025-01-29) |
| Primary citation | Crone, K.K.,Labonte, J.W.,Elias, M.H.,Freeman, M.F. alpha-N-Methyltransferase regiospecificity is mediated by proximal, redundant enzyme-substrate interactions. Protein Sci., 34:e70021-e70021, 2025 Cited by PubMed Abstract: N-Methylation of the peptide backbone confers pharmacologically beneficial characteristics to peptides that include greater membrane permeability and resistance to proteolytic degradation. The borosin family of ribosomally synthesized and post-translationally modified peptides offer a post-translational route to install amide backbone α-N-methylations. Previous work has elucidated the substrate scope and engineering potential of two examples of type I borosins, which feature autocatalytic precursors that encode N-methyltransferases that methylate their own C-termini in trans. We recently reported the first discrete N-methyltransferase and precursor peptide from Shewanella oneidensis MR-1, a minimally iterative, type IV borosin that allowed the first detailed kinetic analyses of borosin N-methyltransferases. Herein, we characterize the substrate scope and resilient regiospecificity of this discrete N-methyltransferase by comparison of relative rates and methylation patterns of over 40 precursor peptide variants along with structure analyses of nine enzyme-substrate complexes. Sequences critical to methylation are identified and demonstrated in assaying minimal peptide substrates and non-native peptide sequences for assessment of secondary structure requirements and engineering potential. This work grants understanding towards the mechanism of substrate recognition and iterative activity by discrete borosin N-methyltransferases. PubMed: 39840790DOI: 10.1002/pro.70021 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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