9SOT
CorZ in complex with SAH, Methyltransferase
Summary for 9SOT
| Entry DOI | 10.2210/pdb9sot/pdb |
| Descriptor | Class I SAM-dependent methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total) |
| Functional Keywords | corz in complex with sah, methyltransferase, myxarylin methyltransferase, biosynthetic protein |
| Biological source | corallococcus coralloides |
| Total number of polymer chains | 3 |
| Total formula weight | 95280.25 |
| Authors | |
| Primary citation | Sikandar, A.,Vianey, L.,Schliessmann, K.,Shen, Q.,Mackay, C.L.,Haeckl, F.P.J.,Urlacher, V.B.,Naismith, J.H.,Muller, R. Myxarylin: Total In Vitro Biosynthesis, Expansion of Substrate Scope, and Bioengineered Thioamidated Biarylitides. J.Am.Chem.Soc., 148:6970-6980, 2026 Cited by PubMed Abstract: Biarylitides are a new class of ribosomally synthesized and post-translationally modified peptides (RiPPs) featuring the smallest reported precursor peptide and cytochrome P450-mediated cross-links. Here, we report the complete reconstitution of the myxobacterial biarylitide, myxarylin. We demonstrate that cross-linking is the first step and acts as a gatekeeper for downstream processing. The cytochrome P450 enzyme P450 from the myxarylin biosynthetic gene cluster exhibits remarkable substrate tolerance, allowing biosynthesis of new-to-nature thioamidated biarylitides through an unprecedented modular precursor peptide engineering approach. Surprisingly, changes in the precursor peptide sequence resulted in a shift in the installation of the P450-mediated modification from the expected C- to the N-terminus. Leader peptide removal follows cross-linking and is likely carried out by a prolyl oligopeptidase (POP), a member of the serine protease family. The last step of the pathway involves N-terminal methylation, which also prevents premature degradation of the pathway intermediates by the POP. The crystal structure of the methyltransferase in complex with SAH and myxarylin allowed us to rationalize its substrate selectivity and guide protein engineering to expand its substrate scope. PubMed: 41687121DOI: 10.1021/jacs.5c17257 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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