Structure of cytochrome oxidase from beef heart mitochondria

In the initial view, one monomer from the dimer in the crystallographic structure is shown as a backbone model, colored according to secondary structure (helix - pink; sheet - orange; coil - gray). The N-side (cytochrome c interface) is up, and the two coppers of CuA can be seen as cyan spacefilling spheres, close to the surface. The hemes are ball and stick models, colored green.

Show Richardson cartoon in original configuration.

Reset initial configuration with wireframe model, colored by chain.

    The protein, showing subunits

  1. The protein structure is shown as a Ca-backbone, colored by chain, with SU I dark blue, SU II, magenta, and the remaining subunits colored in rainbow sequence from blue to red. The heme groups are shown as wireframe models, and the metal centers as spacefilling models.
  2. Show the protein as a spacefilling model, with residues colored by polarity. Hydrophobic residues are white, neutral polar residues are green, basic residues are blue, acidic residues are red.
  3. Show the protein as a spacefilling model, colored by chain.

  4. Rotate 90o about x-axis. Rotate -90o about x-axis.
  5. Rotate 90o about y-axis. Rotate -90o about y-axis.
  6. Rotate 90o about z-axis. Rotate -90o about z-axis.

    The prosthetic groups, showing ligands

  7. The two heme a groups are shown as wireframe models, with heme a3 in red, and heme a in orange. Ligands (see below) are shown as wireframe residues in CPK-colors.
  8. The Tyr244 - His 240 pair, which Yoshikawa thinks form a covalent bond, shown as spacefilling models.

    Mechanism

  9. Residues thought to be involved in the proton transfer mechanism are shown as spacefilled structures in CPK-colors, with numbers at the Cb-position. Orange spacfilled residues show a conformational change on the red-ox transition (Yoshikawa, 1997, personal communication). It has been suggested by Michel and colleagues on the basis of mutagenesis experiments, that His-290 (His-333 in the E. coli sequence) flips between the liganding position shown (where it is also H-bonded to Thr-309), and a H-bonding position with the formyl group of the heme a3, as part of a cycle of protonation and deprotonation linked to the redox chemistry at the binuclear center. In the latter position, the histidine can deliver protons to Asp-364, which forms a salt-bridge with the heme a3 propionate sidechain, and is on the proton output channel. Lys-319 is in the proton delivery channel for the "scalar" protons (those involved in the reduction of O2). Glu242 is thought to be in the "pumped" proton input channel.
  10. A more detailed look at the D and K channel residues. Also shown is another putative H+-channel (the H-channel) identified by Yoshikawa (2000, personal communication) in the bovine complex. The residues are not conserved in bacteria, so the role of this channel is controversial, and considered unlikely to be important by workers studying bacterial enzymes.

    Liganding side chains

    (numbering for both structures available is shown to facilitate comparison) 
    	Beef		Paracoccus

CuB:
(517, SU I (chain A))
His 	240		276
His 	290		325
His 	291		326

Hem a3:
(516 SU I (chain A))
His 	376		411

Hem a
(515 SU I (chain A))
His 	 61		 94
His 	378		413

CuA  
(228, 229 SU II (chain B))
His	161		181
Cys	196		216
Glu	198		218
Cys	200		220
Hhis	204		224
Met	207		227
Trp	104		121

    Reference

    Tsukihara, T., Aoyama, H., Yamashita, E., Tomizaki, T., Yamaguchi, H., Shinzawa-ltoh, K., Nakashima, R., Yaono, R. & Yoshikawa, S. (1996) The Whole Structure of the 13-Subunit Oxidized Cytochrome c Oxidase at 2.5 A. Science 272, 1136-1144.
    ©Copyright 1996, Antony Crofts, University of Illinois at Urbana-Champaign, a-crofts@uiuc.edu