COPPER CAUGHT BINDING NO, O2 | May 10, 2004 Issue - Vol. 82 Issue 19 | Chemical & Engineering News
Volume 82 Issue 19 | p. 11 | News of The Week
Issue Date: May 10, 2004

COPPER CAUGHT BINDING NO, O2

Department: Science & Technology
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À LA MODE
The novel Cu–O2 complex (left) was observed in the active site of a monooxygenase enzyme, while the unusual Cu–NO complex (right) was trapped in the active site of nitrite reductase. Copper is shown in green, nitrogen in blue, oxygen in red, carbon in gray, and sulfur in yellow. The teal ball in the structure on the right represents a water molecule.
Credit: ADAPTED WITH PERMISSION FROM SCIENCE © 2004
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À LA MODE
The novel Cu–O2 complex (left) was observed in the active site of a monooxygenase enzyme, while the unusual Cu–NO complex (right) was trapped in the active site of nitrite reductase. Copper is shown in green, nitrogen in blue, oxygen in red, carbon in gray, and sulfur in yellow. The teal ball in the structure on the right represents a water molecule.
Credit: ADAPTED WITH PERMISSION FROM SCIENCE © 2004

X-ray crystal structures of two different copper-containing metalloenzymes have revealed novel metal adducts of nitric oxide (NO) and oxygen that may be key intermediates in these enzymes’ catalytic mechanisms. The ways in which NO and O2 bind to copper in the active sites of these two enzymes have not previously been seen in nature.

A team led by structural biologists Michael E. P. Murphy and Elitza I. Tocheva of the University of British Columbia, Vancouver, trapped the novel Cu–NO complex in NO-saturated crystals of nitrite reductase, a bacterial enzyme that produces NO from nitrite [Science, 304, 867 (2004)]. The NO molecule is bound “side on” to the enzyme’s copper atom—that is, the nitrogen and oxygen atoms are nearly equidistant from the copper in the 1.3-Å X-ray structure. This unusual Cu–NO binding mode is unprecedented in both synthetic and biological systems, Murphy says.

The unusual Cu–O2 complex was observed in a 1.85-Å X-ray structure of peptidylglycine-alpha-hydroxylating monooxygenase, a copper enzyme involved in peptide hormone processing [Science, 304, 864 (2004)]. In this structure, which was solved by structural biologist L. Mario Amzel and Sean T. Prigge of Johns Hopkins University School of Medicine and coworkers, an O2 molecule is bound to one of the enzyme’s copper atoms via just one of its oxygen atoms. Although theoretical and experimental studies of synthetic copper complexes have suggested that such “end-on” coordination of O2 to Cu is possible, this is the first time anyone’s been able to capture a structural picture of Cu binding O2 in this way.

Novelties aside, these copper adducts “could be important catalytic intermediates,” notes bioinorganic chemist William B. Tolman of the University of Minnesota, Minneapolis.

Amzel and Prigge point out that their observation of the end-on Cu–O2 complex implies that O2 is directly involved in the electron-transfer and hydrogen-abstraction steps of the reaction catalyzed by the monooxygenase. It may even play a role in the reactions of other oxygen-activating copper enzymes, they suggest.

Nitrite reductase may use a side-on Cu–NO complex to change from copper-oxygen to copper-nitrogen coordination during conversion of NO2 to NO, Murphy notes. In addition, “side-on binding may explain the biology of nitric oxide reactions with copper sites in superoxide dismutase and prion proteins,” he says.

 
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