Structural analysis of an open active site conformation of nonheme iron halogenase CytC3

• Main Authors: Wong, Cintyu (Contributor), Fujimori, Danica Galonic (Author), Walsh, Christopher T. (Author), Drennan, Catherine L. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Chemistry (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society, 2011-06-29T19:09:34Z.
• Subjects: Article
• Online Access: Get fulltext

 CytC3, a member of the recently discovered class of nonheme Fe(II) and R-ketoglutarate (RKG)- 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)-RKG-dependentenzymes that catalyze hydroxylation reactions, halogenases catalyze a transfer of halides. To examinethe important enzymatic features that discriminate between chlorination and hydroxylation, the crystal structures of CytC3 both with and without RKG/Fe(II) have been solved to 2.2 Å 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 FesCl 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.