Structure and mechanism of the aberrant ba3-cytochrome c oxidase from Thermus thermophilus

Abstract

Cytochrome c oxidase is a respiratory enzyme catalysing the energy‐conserving reduction of molecular oxygen to water. The crystal structure of the ba3‐cytochrome c oxidase from Thermus thermophilus has been determined to 2.4 Å resolution using multiple anomalous dispersion (MAD) phasing and led to the discovery of a novel subunit IIa. A structure‐based sequence alignment of this phylogenetically very distant oxidase with the other structurally known cytochrome oxidases leads to the identification of sequence motifs and residues that seem to be indispensable for the function of the haem copper oxidases, e.g. a new electron transfer pathway leading directly from CuA to CuB. Specific features of the ba3‐oxidase include an extended oxygen input channel, which leads directly to the active site, the presence of only one oxygen atom (O2−, OH− or H2O) as bridging ligand at the active site and the mainly hydrophobic character of the interactions that stabilize the electron transfer complex between this oxidase and its substrate cytochrome c. New aspects of the proton pumping mechanism could be identified.

Tryptophan-scanning Mutagenesis in the αM3 Transmembrane Domain of the Muscle-type Acetylcholine Receptor

“…positions ␣Val-285 through ␣Ile-289) is consistent with a 3 10 helical motif (61). Similar oscillatory patterns of 3 10 helical structures containing 3-6 amino acids have been found in membrane-spanning domains of several membrane protein structures such as complex (oxireductase/antibody) (62,63), hydrolase (64, 65), lipid transporter (66), mechanosensitive channel (67), membrane protein (68), oxidoreductase (69), oxireductase (70,71), photosynthesis protein (72), signaling protein (73)(74)(75)(76)(77), and transport protein (78). The irregular oscillatory pattern presented at the ends of the periodicity profile for the closed state suggests a disorganized helical structure of the ␣M3 domain.…”

Regulation of the aerobic respiratory chain in the facultatively aerobic and hyperthermophilic archaeon Pyrobaculum oguniense

“…These are located in putative transmembrane helices II and X for the low-spin haem (PoxC: H71, H390; and PoxI: H59, H373) and in helices VI, VII and X for the high-spin haem and the copper ion (PoxC: H252, H302, H303, H388; and PoxI: H219, H268, H269, H371) as found for well-investigated terminal oxidases of known structure (Abramson et al, 2000;Chepuri et al, 1990;Iwata et al, 1995;Santana et al, 2001;Soulimane et al, 2000;Tsubaki et al, 1994). The residues for the K channel of proton pumping are conserved in both oxidases (PoxC: Y257, S268, S328, K331; and PoxI: Y223, S234, S295, Y299).…”

Crystal structures of nitric oxide reductases provide key insights into functional conversion of respiratory enzymes

“…Some protons are used for the catalytic O 2 reduction at the active center, and the other protons are further transferred to the outside of the membrane through proton pumping pathway(s) which is not clearly identified yet. B-type ba 3 COX only has well-defined one proton transfer pathway analogous to Kpathway in A-type COX for the O 2 reduction and proton pumping (20). Similar single proton transfer pathway (K-pathway) is also suggested in C-type cbb 3 COX (16).…”

“…Most recently, Gennis and coworkers reported the functional importance of the Ca ion in C-type cbb 3 COX (17), indicating that structural and functional aspects of the Ca ion are conserved between NORs and C-type COX. In Aand B-type COXs, on the other hand, positively charged groups from two conserved arginine residues locate at the equivalent position to the Ca ion (18)(19)(20)(21). It is therefore likely that NORs and C-type COX are closely related to one another and are evolutionary distinct from A-and B-type COXs, which is consistent with the view from the phylogenetic analysis (7,22).…”

“…The hydrophilic domain exhibits cytochrome c fold in Ctype COX, cNOR, and even in qNOR which does not have heme c (13,14,16), whereas corresponding hydrophilic domain shows cupredoxin fold in A-and B-type COXs (18)(19)(20)(21). Analysis on the structural homology of cytochrome c domains suggests possible evolutional link in NORs and C-type COX.…”