Dataset Information

Enzymatic activation of the nitrogen atom in peptide bonds

ABSTRACT: Abstract The peptide bond is the defining feature of proteins, it co ntrols their structure by enforcing planarity and governs their chemistry by abolishing nucleophili city. This behaviour results from the delocalisation of the lone pair of electrons on the nitrogen atom into the adjacent carbonyl bond. Methylating an amide bond by conventional chemistry usually requires a metal to generate the amide anion. The OphA enzyme methyla tes amide bonds at pH 7 in water using S-adenosyl methionine (SAM) as co-factor. The st ructure of OphA reveals a complex catenane arrangement in which the substrate i s clamped adjacent to SAM. Site directed mutants have identified the key catalytic residue s. A mechanism in which conjugation of the peptide bond is disrupted by van der Waals in teractions between SAM and the amide nitrogen is proposed and tested. The methylation of amides is of particular interest as it greatly enhances the cell permeability of peptides.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Escherichia Coli

SUBMITTER: Sally Shirran

LAB HEAD: Sally Lorna Shirran

PROVIDER: PXD005934 | Pride | 2020-03-20

REPOSITORIES: Pride

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

Song Haigang H van der Velden Niels S NS Shiran Sally L SL Bleiziffer Patrick P Zach Christina C Sieber Ramon R Imani Aman S AS Krausbeck Florian F Aebi Markus M Freeman Michael F MF Riniker Sereina S Künzler Markus M Naismith James H JH

Science advances 20180824 8

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 <i>S</i>-adenosyl ...[more]

PMID: 30151425

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			Action	DRS
	BMS_170213.fasta	Fasta
	F017898.mzid.gz	Mzid
	F017898.pride.mztab.gz	Mztab
	F017899.mzid.gz	Mzid
	F017899.pride.mztab.gz	Mztab