Structural Basis for Methine Excision by a Heme Oxygenase-like Enzyme

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Heme oxygenase-like domain-containing oxidases (HDOs) are a rapidly expanding enzyme family that typically use dinuclear metal cofactors instead of heme. FlcD, an HDO from the opportunistic pathogen Pseudomonas aeruginosa, catalyzes the excision of an oxime carbon in the biosynthesis of the copper-containing antibiotic fluopsin C. We show that FlcD is a dioxygenase that catalyzes a four-electron oxidation. Crystal structures of FlcD reveal a mononuclear iron in the active site, which is coordinated by two histidines, one glutamate, and the oxime of the substrate. Enzyme activity, Mössbauer spectroscopy, and electron paramagnetic resonance spectroscopy analyses support the usage of a mononuclear iron cofactor. This cofactor resembles that of mononuclear non-heme iron-dependent enzymes and breaks the paradigm of dinuclear HDO cofactors. This study begins to illuminate the catalytic mechanism of methine excision and indicates convergent evolution of different lineages of mononuclear iron-dependent enzymes.
Funding Information
  • Searle Scholars Program
  • National Institute of Child Health and Human Development (DP2HD094657)
  • Division of Graduate Education (DGE-1650116)
  • David and Lucile Packard Foundation
  • National Institute of General Medical Sciences (GM111978, GM126303, GM137286, R01GM148685, T32GM008570, T32GM135122)

This publication has 56 references indexed in Scilit: