PDBsum entry 1v55

Oxidoreductase

PDB id: 1v55

Contents

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. *

Ligands

HEA ×4

TGL ×6

PGV ×8

CUA ×2

CHD ×8

CDL ×4

PEK ×6

UNX ×2

PSC ×2

DMU ×2

Metals

_ZN ×2

_CU ×2

_MG ×2

_NA ×2

Waters ×1943

* Residue conservation analysis

PDB id:

1v55

Name:

Oxidoreductase

Title:

Bovine heart cytochromE C oxidase at the fully reduced state

Structure:

CytochromE C oxidase polypeptide i. Chain: a, n. CytochromE C oxidase polypeptide ii. Chain: b, o. CytochromE C oxidase polypeptide iii. Chain: c, p. CytochromE C oxidase subunit iv isoform 1. Chain: d, q. Synonym: cox iv-1, cytochromE C oxidase polypeptide iv.

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Tissue: heart. Tissue: heart

Biol. unit:

26mer (from PQS)

Resolution:

1.90Å R-factor: 0.203 R-free: 0.230

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

Key ref:

T.Tsukihara et al. (2003). The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process. Proc Natl Acad Sci U S A, 100, 15304-15309. PubMed id: 14673090 DOI: 10.1073/pnas.2635097100

Date:

21-Nov-03 Release date: 23-Dec-03

Protein chains

P00396  (COX1_BOVIN) -  Cytochrome c oxidase subunit 1 from Bos taurus

Seq: 514 a.a.

Struc: 514 a.a.*

Protein chains

P68530  (COX2_BOVIN) -  Cytochrome c oxidase subunit 2 from Bos taurus

Seq: 227 a.a.

Struc: 227 a.a.*

Protein chains

P00415  (COX3_BOVIN) -  Cytochrome c oxidase subunit 3 from Bos taurus

Seq: 261 a.a.

Struc: 259 a.a.

Protein chains

P00423  (COX41_BOVIN) -  Cytochrome c oxidase subunit 4 isoform 1, mitochondrial from Bos taurus

Seq: 169 a.a.

Struc: 144 a.a.

Protein chains

P00426  (COX5A_BOVIN) -  Cytochrome c oxidase subunit 5A, mitochondrial from Bos taurus

Seq: 152 a.a.

Struc: 105 a.a.

Protein chains

P00428  (COX5B_BOVIN) -  Cytochrome c oxidase subunit 5B, mitochondrial from Bos taurus

Seq: 129 a.a.

Struc: 98 a.a.

Protein chains

P07471  (CX6A2_BOVIN) -  Cytochrome c oxidase subunit 6A2, mitochondrial from Bos taurus

Seq: 97 a.a.

Struc: 84 a.a.*

Protein chains

P00429  (CX6B1_BOVIN) -  Cytochrome c oxidase subunit 6B1 from Bos taurus

Seq: 86 a.a.

Struc: 79 a.a.

Protein chains

P04038  (COX6C_BOVIN) -  Cytochrome c oxidase subunit 6C from Bos taurus

Seq: 74 a.a.

Struc: 73 a.a.*

Protein chains

P07470  (CX7A1_BOVIN) -  Cytochrome c oxidase subunit 7A1, mitochondrial from Bos taurus

Seq: 80 a.a.

Struc: 58 a.a.

Protein chains

P13183  (COX7B_BOVIN) -  Cytochrome c oxidase subunit 7B, mitochondrial from Bos taurus

Seq: 80 a.a.

Struc: 49 a.a.

Protein chains

P00430  (COX7C_BOVIN) -  Cytochrome c oxidase subunit 7C, mitochondrial from Bos taurus

Seq: 63 a.a.

Struc: 46 a.a.

Protein chains

P10175  (COX8B_BOVIN) -  Cytochrome c oxidase subunit 8B, mitochondrial from Bos taurus

Seq: 70 a.a.

Struc: 43 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, N, O, P: E.C.7.1.1.9 - cytochrome-c oxidase.
• Reaction: 4 Fe(II)-[cytochrome c] + O2 + 8 H⁺(in) = 4 Fe(III)-[cytochrome c] + 2 H2O + 4 H⁺(out)
• Cofactor: Cu cation

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1073/pnas.2635097100

Proc Natl Acad Sci U S A 100:15304-15309 (2003)

PubMed id: 14673090

The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process.

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.

ABSTRACT

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.

Selected figure(s)

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.

Figures were selected by an automated process.