Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis

• Published in: Nature 2006-03, Vol.440 (7082), p.368-371
• Main Authors: Blasiak, L.C, Vaillancourt, F.H, Walsh, C.T, Drennan, C.L
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - biosynthesis; Bacterial Proteins - chemistry; Binding Sites; Biological and medical sciences; Biosynthesis; Chlorides - metabolism; Chlorination; Crystal structure; Crystalline structure; Crystallography, X-Ray; Deoxyribonucleic acid; DNA; Enzymes; Fundamental and applied biological sciences. Psychology; Genetics; Halogenation; Histidine - metabolism; Humanities and Social Sciences; Hypoxia; Iron; Iron - metabolism; Ketoglutaric Acids - metabolism; letter; Ligands; Mammals; Models, Molecular; Molecular biophysics; multidisciplinary; non-heme iron halogenase; Oxidoreductases - chemistry; Oxidoreductases - metabolism; plant pathogenic bacteria; Protein Conformation; Pseudomonas syringae - classification; Pseudomonas syringae - enzymology; Pseudomonas syringae - metabolism; Pseudomonas syringae pv. syringae; Science; Science (multidisciplinary); Structure in molecular biology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature04544

Non-haem Fe(ii)/α-ketoglutarate (αKG)-dependent enzymes harness the reducing power of αKG to catalyse oxidative reactions, usually the hydroxylation of unactivated carbons, and are involved in processes such as natural product biosynthesis, the mammalian hypoxic response, and DNA repair. These enzymes couple the decarboxylation of αKG with the formation of a high-energy ferryl-oxo intermediate that acts as a hydrogen-abstracting species. All previously structurally characterized mononuclear iron enzymes contain a 2-His, 1-carboxylate motif that coordinates the iron. The two histidines and one carboxylate, known as the 'facial triad', form one triangular side of an octahedral iron coordination geometry. A subclass of mononuclear iron enzymes has been shown to catalyse halogenation reactions, rather than the more typical hydroxylation reaction. SyrB2, a member of this subclass, is a non-haem Fe(ii)/αKG-dependent halogenase that catalyses the chlorination of threonine in syringomycin E biosynthesis. Here we report the structure of SyrB2 with both a chloride ion and αKG coordinated to the iron ion at 1.6 Å resolution. This structure reveals a previously unknown coordination of iron, in which the carboxylate ligand of the facial triad is replaced by a chloride ion.