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

被引:279
作者
Blasiak, LC
Vaillancourt, FH
Walsh, CT
Drennan, CL [1 ]
机构
[1] MIT, Dept Chem, Cambridge, MA 02139 USA
[2] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
基金
美国国家卫生研究院; 加拿大自然科学与工程研究理事会;
关键词
D O I
10.1038/nature04544
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Non- haem Fe( II)/ alpha-ketoglutarate ( alpha KG)- dependent enzymes harness the reducing power of alpha KG 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(1,2). These enzymes couple the decarboxylation of alpha KG with the formation of a high- energy ferryl- oxo intermediate that acts as a hydrogen- abstracting species(2-4). All previously structurally characterized mononuclear iron enzymes contain a 2- His, 1- carboxylate motif that coordinates the iron(1,2). 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(5,6). SyrB2, a member of this subclass, is a non- haem Fe( II)/ alpha KG-dependent halogenase that catalyses the chlorination of threonine in syringomycin E biosynthesis(5). Here we report the structure of SyrB2 with both a chloride ion and alpha KG coordinated to the iron ion at 1.6 angstrom 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.
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页码:368 / 371
页数:4
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