page_title: Tryptophan 7-halogenase
section_title: Structure
hierarchical_section_title: Tryptophan 7-halogenase / Structure
caption_attribution_description: English: Illustration of FAD, Cl-, and W in PrnA
context_page_description: Tryptophan 7-halogenase is an enzyme with systematic name L-tryptophan:FADH2 oxidoreductase. This enzyme catalyses the following chemical reaction:
  tryptophan + FADH₂ + Cl⁻ + O₂ + H⁺ 7-chloro-L-tryptophan + FAD + 2 H₂O
  The enzyme can use bromide ions in place of chloride.
context_section_description: Tryptophan 7-halogenase is a 538-residue, 61-kDa protein. In solution, a number of homologues exist as homodimers.
  The enzyme has two main binding sites: one for FAD and one for tryptophan. Note that the FAD is supplied by a separate flavin reductase which may be a general enzyme recruited from metabolism or a specific enzyme encoded in the relevant biosynthetic gene cluster. The former site is also the site of reaction for the oxidation of FAD by O₂. Connecting these two sites is a tunnel-like structure approximately 10 Å in length. The FAD binding site also binds a single chloride ion. A chlorinating agent is generated at the FAD-binding site, then channeled through this tunnel where it reacts with the substrate tryptophan. Tryptophan is bound by a number of interactions: other aromatic amino acid residues such as tryptophan, phenylalanine, and histidine seemingly "sandwich" the substrate, the N-H group of tryptophan forms hydrogen bonding interactions with the peptide backbone of the enzyme, and the amino acid moiety of tryptophan interacts with nearby tyrosine and glutamate residues. It is thought that the regioselectivity of the enzyme is a consequence of the spatial orientation of the tryptophan, with C7 placed close to the end of the tunnel where the chlorinating agent exits. Multiple halogenations are prevented as the addition of a halogen atom to the substrate greatly increases its steric bulk, causing it to dissociate from the enzyme.
caption: Tryptophan 7-halogenase with bound substrates: FAD (red), chloride anion (green), and tryptophan (yellow). (PDB: 2AQJ​)
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