6GEW
OphA Y63F-sinefungin complex
Summary for 6GEW
| Entry DOI | 10.2210/pdb6gew/pdb |
| Descriptor | OphA, S-ADENOSYL-L-HOMOCYSTEINE, SINEFUNGIN, ... (4 entities in total) |
| Functional Keywords | peptide n-transferase, transferase |
| Biological source | Omphalotus olearius |
| Total number of polymer chains | 1 |
| Total formula weight | 45763.96 |
| Authors | Song, H.,Naismith, J.H. (deposition date: 2018-04-27, release date: 2018-09-19, Last modification date: 2024-01-17) |
| Primary citation | Song, H.,van der Velden, N.S.,Shiran, S.L.,Bleiziffer, P.,Zach, C.,Sieber, R.,Imani, A.S.,Krausbeck, F.,Aebi, M.,Freeman, M.F.,Riniker, S.,Kunzler, M.,Naismith, J.H. A molecular mechanism for the enzymatic methylation of nitrogen atoms within peptide bonds. Sci Adv, 4:eaat2720-eaat2720, 2018 Cited by PubMed Abstract: The peptide bond, the defining feature of proteins, governs peptide chemistry by abolishing nucleophilicity of the nitrogen. This and the planarity of the peptide bond arise from the delocalization of the lone pair of electrons on the nitrogen atom into the adjacent carbonyl. While chemical methylation of an amide bond uses a strong base to generate the imidate, OphA, the precursor protein of the fungal peptide macrocycle omphalotin A, self-hypermethylates amides at pH 7 using -adenosyl methionine (SAM) as cofactor. The structure of OphA reveals a complex catenane-like arrangement in which the peptide substrate is clamped with its amide nitrogen aligned for nucleophilic attack on the methyl group of SAM. Biochemical data and computational modeling suggest a base-catalyzed reaction with the protein stabilizing the reaction intermediate. Backbone N-methylation of peptides enhances their protease resistance and membrane permeability, a property that holds promise for applications to medicinal chemistry. PubMed: 30151425DOI: 10.1126/sciadv.aat2720 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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