Wong Cintyu, Fujimori Danica Galonić, Walsh Christopher T, Drennan Catherine L
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, Massachusetts 02139, USA.
J Am Chem Soc. 2009 Apr 8;131(13):4872-9. doi: 10.1021/ja8097355.
CytC3, a member of the recently discovered class of nonheme Fe(II) and alpha-ketoglutarate (alphaKG)-dependent halogenases, catalyzes the double chlorination of L-2-aminobutyric acid (Aba) to produce a known Streptomyces antibiotic, gamma,gamma-dichloroaminobutyrate. Unlike the majority of the Fe(II)-alphaKG-dependent enzymes that catalyze hydroxylation reactions, halogenases catalyze a transfer of halides. To examine the important enzymatic features that discriminate between chlorination and hydroxylation, the crystal structures of CytC3 both with and without alphaKG/Fe(II) have been solved to 2.2 A resolution. These structures capture CytC3 in an open active site conformation, in which no chloride is bound to iron. Comparison of the open conformation of CytC3 with the closed conformation of another nonheme iron halogenase, SyrB2, suggests two important criteria for creating an enzyme-bound Fe-Cl catalyst: (1) the presence of a hydrogen-bonding network between the chloride and surrounding residues, and (2) the presence of a hydrophobic pocket in which the chloride resides.
CytC3是最近发现的一类非血红素铁（II）和α-酮戊二酸（αKG）依赖性卤化酶的成员，它催化L-2-氨基丁酸（Aba）的双氯化反应，生成一种已知的链霉菌抗生素γ，γ-二氯氨基丁酸酯。与大多数催化羟基化反应的铁（II）-αKG依赖性酶不同，卤化酶催化卤化物的转移。为了研究区分氯化和羟基化的重要酶学特征，已解析了有和没有αKG/铁（II）时CytC3的晶体结构，分辨率达到2.2埃。这些结构捕获到处于开放活性位点构象的CytC3，其中没有氯离子与铁结合。将CytC3的开放构象与另一种非血红素铁卤化酶SyrB2的封闭构象进行比较，提出了形成酶结合铁-氯催化剂的两个重要标准：（1）氯离子与周围残基之间存在氢键网络，（2）存在氯离子所在的疏水口袋。
