page_title: Formylation
section_title: Mechanism
hierarchical_section_title: Formylation / Formylation reactions in biology / Formylation reactions in purine biosynthesis / GAR transformylase / Mechanism
caption_attribution_description: English: Mechanism of the enzyme PurN GAR transformylase
context_page_description: In biochemistry, the addition of a formyl functional group is termed formylation. A formyl functional group consists of a carbonyl bonded to hydrogen. When attached to an R group, a formyl group is called an aldehyde.
  Formylation has been identified in several critical biological processes. Methionine was first discovered to be formylated in E. coli by Marcker and Sanger in 1964 and was later identified to be involved in the initiation of protein synthesis in bacteria and organelles. The formation of N-formylmethionine is catalyzed by the enzyme methionyl-tRNAᴹᵉᵗ transformylase. Additionally, two formylation reactions occur in the de novo biosynthesis of purines. These reactions are catalyzed by the enzymes glycinamide ribonucleotide transformylase and 5-aminoimidazole-4-carboxyamide ribotide transformylase. More recently, formylation has been discovered to be a histone modification, which may modulate gene expression.
context_section_description: The formylation reaction is proposed to occur through a direct transfer reaction in which the amine group of GAR nucleophillically attacks N10-formyl-THF creating a tetrahedral intermediate. As the α-amino group of GAR is relatively reactive, deprotonation of the nucleophile is proposed to occur by solvent. In the active site, Asn 106, His 108, and Asp 144 are positioned to assist with formyl transfer. However, mutagenesis studies have indicated that these residues are not individually essential for catalysis, as only mutations of two or more residues inhibit the enzyme. Based on the structure the negatively charged Asp144 is believed to increase the pKa of His108, allowing the protonated imidazolium group of His108 to enhances the electrophillicity of the N10-formyl-THF formyl group. Additionally, His108 and Asn106 are believed to stabilize the oxyanion formed in the transition state.
caption: Mechanism of PurN GAR transformylase
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