Adenosyl-fluoride synthase

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Adenosyl-fluoride synthase
Identifiers
EC number 2.5.1.63
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

In enzymology, an adenosyl-fluoride synthase (EC 2.5.1.63) is an enzyme that catalyzes the chemical reaction

S-adenosyl-L-methionine + fluoride \rightleftharpoons 5'-deoxy-5'-fluoroadenosine + L-methionine

Thus, the two substrates of this enzyme are S-adenosyl-L-methionine, (SAM) and fluoride, whereas its two products are 5'deoxy-5'-fluoroadenosine and L-methionine. The fluorinated product is used to synthesise 4-fluorothreonine (4-FT), which is an antibiotic used to destroy other micro-organisms.

This enzyme belongs to the family of transferases, specifically those transferring aryl or alkyl groups other than methyl groups. The systematic name of this enzyme class is S-adenosyl-L-methionine:fluoride adenosyltransferase. This enzyme is also called fluorinase and 5-Flouro-deoxyadenosine synthase.

Structural studies[edit]

As of late 2007, 9 structures have been solved for this class of enzymes, with PDB accession codes 1RQP, 1RQR, 2C2W, 2C4T, 2C4U, 2C5B, 2C5H, 2CBX, and 2CC2.

The names given to the enzyme come not from the structure, but from the function: 5-Fluoro-5-deoxyadenosine is the molecule synthesised. The structure is homologous to the duf-62 enzyme series. The enzyme is a dimer of trimers (2 molecules each with three subunits). The active sites are located between these subunits (subunit interfaces), each can bind to one SAM molecule at a time.[1]

Reactivity[edit]

The Fluorinase catalyses a nucleophilic substitution stage, this is a single step bimolecular process (SN2). The fluoride attacks a secondary carbon atom, with the methionine as the leaving group. The process will not occur at an appreciable rate without the enzyme because the Fluoride nucleophile is deactivated in the aqueous environment in which it exists in cells. It has been shown that the mechanism will work too for chloride ions, though the fluorinase has a preference for the fluoride ion.[1]

The Fluorinase catalysed substitution of S-Adenosyl Methionine 'curly arrow' mechanism.













See also[edit]

References[edit]

  1. ^ a b Dong, C (2004). "Crystal Structure and Mechanism of a Bacterial Flourinating Enzyme". Nature Chem. 427: 561–565. doi:10.1038/nature02280. 
  • O'Hagan D, Schaffrath C, Cobb SL, Hamilton JT, Murphy CD (2002). "Biochemistry: biosynthesis of an organofluorine molecule". Nature. 416 (6878): 279. doi:10.1038/416279a. PMID 11907567. 
  • Naismith JH; Huang, F; Deng, H; Schaffrath, C; Spencer, JB; O'Hagan, D; Naismith, JH (2004). "Crystal structure and mechanism of a bacterial fluorinating enzyme". Nature. 427 (6974): 561–5. doi:10.1038/nature02280. PMID 14765200.