PDBsum entry 1v54

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Oxidoreductase PDB id
Protein chains
514 a.a. *
227 a.a. *
259 a.a. *
144 a.a. *
105 a.a. *
98 a.a. *
84 a.a. *
79 a.a. *
73 a.a. *
58 a.a. *
49 a.a. *
46 a.a. *
43 a.a. *
HEA ×4
TGL ×6
PGV ×8
CUA ×2
CHD ×8
CDL ×4
PEK ×6
UNX ×2
PSC ×2
DMU ×2
_ZN ×2
_CU ×2
_MG ×2
_NA ×2
Waters ×1970
* Residue conservation analysis

References listed in PDB file
Key reference
Title The low-Spin heme of cytochrome c oxidase as the driving element of the proton-Pumping process.
Authors T.Tsukihara, K.Shimokata, Y.Katayama, H.Shimada, K.Muramoto, H.Aoyama, M.Mochizuki, K.Shinzawa-Itoh, E.Yamashita, M.Yao, Y.Ishimura, S.Yoshikawa.
Ref. Proc Natl Acad Sci U S A, 2003, 100, 15304-15309. [DOI no: 10.1073/pnas.2635097100]
PubMed id 14673090
Mitochondrial cytochrome c oxidase plays an essential role in aerobic cellular respiration, reducing dioxygen to water in a process coupled with the pumping of protons across the mitochondrial inner membrane. An aspartate residue, Asp-51, located near the enzyme surface, undergoes a redox-coupled x-ray structural change, which is suggestive of a role for this residue in redox-driven proton pumping. However, functional or mechanistic evidence for the involvement of this residue in proton pumping has not yet been obtained. We report that the Asp-51 --> Asn mutation of the bovine enzyme abolishes its proton-pumping function without impairment of the dioxygen reduction activity. Improved x-ray structures (at 1.8/1.9-A resolution in the fully oxidized/reduced states) show that the net positive charge created upon oxidation of the low-spin heme of the enzyme drives the active proton transport from the interior of the mitochondria to Asp-51 across the enzyme via a water channel and a hydrogen-bond network, located in tandem, and that the enzyme reduction induces proton ejection from the aspartate to the mitochondrial exterior. A peptide bond in the hydrogen-bond network critically inhibits reverse proton transfer through the network. A redox-coupled change in the capacity of the water channel, induced by the hydroxyfarnesylethyl group of the low-spin heme, suggests that the channel functions as an effective proton-collecting region. Infrared results indicate that the conformation of Asp-51 is controlled only by the oxidation state of the low-spin heme. These results indicate that the low-spin heme drives the proton-pumping process.
Figure 2.
Fig. 2. Redox-coupled conformational changes in Asp-51. (A) Stereoscopic drawing of the hydrogen-bond network in the fully oxidized and reduced (blue structure) states at 1.8- and 1.9-Å resolution, respectively, viewed from the intermembrane side. The two histidines bound to Fe[a] (heme a iron), are not shown. (B) The hydrogen-bonding structure of Asp-51 in the oxidized (Left) and reduced (Right) states. The smooth thick curve denotes the molecular surface to which the water molecules in the intermembrane space are accessible. The conformational changes induced by reduction of the enzyme are shown by blue structures in Right. The blue (A) and black (B) balls represent the fixed water molecules. The dotted lines denote hydrogen bonds. The double-headed dotted arrows show a possible movement of the water molecule from Arg-38 to Tyr-371.
Figure 4.
Fig. 4. Proposed proton-pumping mechanism. The iron, porphyrin, and formyl side group of heme a are shown by Fe[a], Pr, and CHO, respectively. The COOH on Pr denotes one of the propionate groups of heme a. The brackets ([]1+ and[]0) indicate the net charge of the six-coordinated heme a. The diagrams shadowed and in the dotted squares show the structures in the stable and intermediate states, respectively. The thick arrows in a and d-f and the thin arrows in d and e indicate the electrostatic influence of the net positive charge of heme a and the proton transfers upon heme a oxidation, respectively. The dotted lines in the diagrams denote the hydrogen bond network connecting Arg-38 with Asp-51, including the peptide bond that blocks the reverse proton transfer from the intermembrane side.
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