1ZPU

Crystal Structure of Fet3p, a Multicopper Oxidase that Functions in Iron Import

Summary for 1ZPU

• Entry DOI: 10.2210/pdb1zpu/pdb
• Descriptor: Iron transport multicopper oxidase FET3, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: multicopper oxidase, ferroxidase, iron transport, oxidoreductase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Cellular location: Cell membrane; Single-pass type I membrane protein; Extracellular side: P38993
• Total number of polymer chains: 6
• Total formula weight: 398630.31

Authors

Taylor, A.B.,Stoj, C.S.,Ziegler, L.,Kosman, D.J.,Hart, P.J. (deposition date: 2005-05-17, release date: 2005-10-04, Last modification date: 2020-07-29)

Primary citation

Taylor, A.B.,Stoj, C.S.,Ziegler, L.,Kosman, D.J.,Hart, P.J.
The copper-iron connection in biology: Structure of the metallo-oxidase Fet3p.
Proc.Natl.Acad.Sci.Usa, 102:15459-15464, 2005

PubMed Abstract: Fet3p is a multicopper-containing glycoprotein localized to the yeast plasma membrane that catalyzes the oxidation of Fe(II) to Fe(III). This ferrous iron oxidation is coupled to the reduction of O(2) to H(2)O and is termed the ferroxidase reaction. Fet3p-produced Fe(III) is transferred to the permease Ftr1p for import into the cytosol. The posttranslational insertion of four copper ions into Fet3p is essential for its activity, thus linking copper and iron homeostasis. The mammalian ferroxidases ceruloplasmin and hephaestin are homologs of Fet3p. Loss of the Fe(II) oxidation catalyzed by these proteins results in a spectrum of pathological states, including death. Here, we present the structure of the Fet3p extracellular ferroxidase domain and compare it with that of human ceruloplasmin and other multicopper oxidases that are devoid of ferroxidase activity. The Fet3p structure delineates features that underlie the unique reactivity of this and homologous multicopper oxidases that support the essential trafficking of iron in diverse eukaryotic organisms. The findings are correlated with biochemical and physiological data to cross-validate the elements of Fet3p that define it as both a ferroxidase and cuprous oxidase.

PubMed: 16230618
DOI: 10.1073/pnas.0506227102

Experimental method

X-RAY DIFFRACTION (2.8 Å)