5N0S

Crystal structure of OphA-DeltaC6 mutant Y98A in complex with SAM


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

A molecular mechanism for the enzymatic methylation of nitrogen atoms within peptide bonds.

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.

(2018) Sci Adv 4: eaat2720-eaat2720

  • DOI: https://doi.org/10.1126/sciadv.aat2720
  • Primary Citation of Related Structures:  
    5N0N, 5N0O, 5N0P, 5N0Q, 5N0R, 5N0S, 5N0T, 5N0U, 5N0V, 5N0W, 5N0X, 5N4I, 5OUF, 6GEW

  • 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 S -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.


  • Organizational Affiliation

    Biomedical Sciences Research Complex, North Haugh, University of St. Andrews, Fife KY16 9ST, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide N-methyltransferase
A, B
410Omphalotus oleariusMutation(s): 0 
UniProt
Find proteins for A0A2R2JFI5 (Omphalotus olearius)
Explore A0A2R2JFI5 
Go to UniProtKB:  A0A2R2JFI5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A2R2JFI5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 163.906α = 90
b = 92.521β = 90
c = 85.332γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-02-14
    Type: Initial release
  • Version 1.1: 2018-09-19
    Changes: Data collection, Database references
  • Version 1.2: 2024-01-17
    Changes: Data collection, Database references, Refinement description