6tsc | pdb_00006tsc

OphMA I407P complex with SAH

spinqualitylabelsall models 6tsc, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6tsc is a 2 chain structure with sequence from Jack o'lantern. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SAH NonStd Res: MVA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The methylation of amide nitrogen atoms can improve the stability, oral availability, and cell permeability of peptide therapeutics. Chemical N-methylation of peptides is challenging. Omphalotin A is a ribosomally synthesized, macrocylic dodecapeptide with nine backbone N-methylations. The fungal natural product is derived from the precursor protein, OphMA, harboring both the core peptide and a SAM-dependent peptide alpha-N-methyltransferase domain. OphMA forms a homodimer and its alpha-N-methyltransferase domain installs the methyl groups in trans on the hydrophobic core dodecapeptide and some additional C-terminal residues of the protomers. These post-translational backbone N-methylations occur in a processive manner from the N- to the C-terminus of the peptide substrate. We demonstrate that OphMA can methylate polar, aromatic, and charged residues when these are introduced into the core peptide. Some of these amino acids alter the efficiency and pattern of methylation. Proline, depending on its sequence context, can act as a tunable stop signal. Crystal structures of OphMA variants have allowed rationalization of these observations. Our results hint at the potential to control this fungal alpha-N-methyltransferase for biotechnological applications. Substrate Plasticity of a Fungal Peptide alpha-N-Methyltransferase.,Song H, Fahrig-Kamarauskaite JR, Matabaro E, Kaspar H, Shirran SL, Zach C, Pace A, Stefanov BA, Naismith JH, Kunzler M ACS Chem Biol. 2020 Jun 19. doi: 10.1021/acschembio.0c00237. PMID:32491837 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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