X-ray structure of cyanide-bound bovine heart cytochromecoxidase in the fully oxidized state at 2.0 Å resolution

Abstract

The X-ray structure of cyanide-bound bovine heart cytochromecoxidase in the fully oxidized state was determined at 2.0 Å resolution. The structure reveals that the peroxide that bridges the two metals in the fully oxidized state is replaced by a cyanide ion bound in a nearly symmetric end-on fashion without significantly changing the protein conformation outside the two metal sites.

Modulation of O2 reduction in Saccharomyces cerevisiae mitochondria

“…The crystal structure of the bovine oxidized Cyt c O shows that the CN − ion bridges between the two metal centers of the catalytic site of Cyt c O . Weaker binding of CN − may, for example, be a consequence of an increase in the distance between the heme a 3 iron and Cu B , which is normally ~ 5 Å .…”

“…Here, we studied effects of binding of cyanide to wild‐type and rcf1 Δ mitochondria to investigate functional consequences of the rcf1 deletion on Cyt c O. Cyanide specifically inhibits Cyt c O by binding to the catalytic site of this enzyme. The structure of the oxidized bovine Cyt c O with bound cyanide indicates that the CN − ion bridges between the iron of heme a 3 and Cu B . In the past, binding of cyanide to the Cyt c O catalytic site has been used as a probe for its structure.…”

Characterisation of the Cyanate Inhibited State of Cytochrome c Oxidase

“…Inhibition of the binuclear center (BNC) has been shown in the past using different organic ions such as cyanide (CN − ), sulfide (S 2− ) or azide (N 3 − , which is isoelectronic to NCO − ) [2][3][4][5][6][7]12,59 . The involved excess electrons in this process could lead to partial heme reduction and consequently to the rise of the Soret band at around 444 nm 60,61 .…”

“…For example, a bridging peroxide (O 2 2− ) has been proposed to exist in the resting state of CcO 1 that requires two more electrons to get fully reduced than the oxidized state during catalytic turnover. Intense research has been performed on cyanide [2][3][4][5][6][7] (CN − ) ligands that effectively block the BNC for oxygen. While this inhibition of CcO is a central subject in medical research on cyanide poisoning [8][9][10][11] , spectroscopic studies on the binding properties of ligands such as cyanide, azide (N 3 − ) or sulphide (S 2− ) 2,12,13 have been performed to derive the oxygen reduction mechanism, to get insight into the structure of the active site 2,5,6,14 and for spectral isolation of the two heme centers [15][16][17][18] .…”

Isolation of yeast complex IV in native lipid nanodiscs

“…Based on a structural model of the S. cerevisiae CytcO [28] or the structure of the bovine heart CytcO [29], the dimension of a CytcO monomer is approximately 7 nm x 9 nm when observed perpendicular to the membrane surface. As indicated above, the approximate dimensions of the isolated SMA-CytcO discs were 11 nm x 14 nm, where the smaller of these numbers, 11 nm, is presumably the "height" of the CytcO.…”