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Dioxygen reduction by multi-copper oxidases; a structural perspective
Isabel Bento1, Lígia O Martins, Gonçalo Gato Lopes
1Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa Apartado 127, Av. República, 2781-901, Oeiras, Portugal. bento@itqb.unl.pt
Dalton Transactions (Cambridge, England : 2003)
|October 20, 2005
Summary
Multi-copper oxidases use a trinuclear copper center to reduce dioxygen to water. Recent X-ray studies of Bacillus subtilis CotA reveal key stages in this multi-copper enzyme mechanism, including peroxide intermediates.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Multi-copper oxidases catalyze substrate oxidation via electron transfer to a trinuclear copper center.
- This center also reduces dioxygen to water, a crucial but mechanistically unclear process.
- The CotA endospore coat protein from Bacillus subtilis is a model system for studying these enzymes.
Purpose of the Study:
- To elucidate the mechanism of dioxygen reduction by multi-copper oxidases.
- To provide structural insights into the key stages of the catalytic cycle.
- To detail a putative mechanism based on new structural data.
Main Methods:
- X-ray crystallography of the CotA protein.
- Analysis of structures in oxidized and reduced states.
- Inclusion of peroxide and azide (inhibitor) to trap intermediates.
Main Results:
- Proposed a mechanism for dioxygen binding within the trinuclear center, near type 2 and type 3 copper ions.
- Identified a peroxide intermediate and subsequent splitting.
- Suggested hydroxide moiety migration towards the solvent exit channel, possibly involving type 2 copper movement.
Conclusions:
- The study provides a detailed putative mechanism for dioxygen reduction by multi-copper oxidases.
- Structural data illuminate the roles of different copper centers and intermediates.
- The findings advance understanding of enzymatic water formation in biological systems.