Authors: Alaina J Terzulli Daniel J Kosman
Publish Date: 2008/11/21
Volume: 14, Issue: 2, Pages: 315-325
Abstract
Multicopper oxidases MCO contain at least four copper atoms arrayed in three distinct ligand fields supported by two canonical structural features 1 multiples of the cupredoxin fold and 2 four unique sequence elements that include the ten histidine and one cysteine ligands to the four copper atoms Ferroxidases are a subfamily of MCO proteins that contain residues supporting a specific reactivity towards ferrous iron these MCOs play a vital role in iron metabolism in bacteria algae fungi and mammals In contrast to the fungal ferroxidases eg Fet3p from Saccharomyces cerevisiae the mammalian ceruloplasmin Cp is twice as large six vs three cupredoxin domains and contains three type 1 or “blue” copper sites Chlamydomonas reinhardtii expresses a putative ferroxidase Fox1 which has sequence similarity to human Cp hCp Eschewing the standard sequencebased modeling paradigm we have constructed a functionbased model of the Fox1 protein which replicates hCp’s six coppersite ligand arrays with an overall root mean square deviation of 14 Å Analysis of this model has led also to assignment of motifs in Fox1 that are unique to ferroxidases the strongest evidence to date that the wellcharacterized fungal highaffinity iron uptake system is essential to iron homeostasis in green algae The model of Fox1 also establishes a subfamily of MCO proteins with a noncanonical copperligand organization These diverse structures suggest alternative mechanisms for intramolecular electron transfer and require a new trajectory for the evolution of the MCO superfamily
Keywords: