Absolute configuration of the hydroxyfarnesylethyl group of haem A, determined by X-ray structural analysis of bovine heart cytochrome<i>c</i>oxidase using methods applicable at 2.8 Å resolution

Yamashita, Eiki; Aoyama, Hiroshi; Yao, Ming; Muramoto, Kazumasa; Shinzawa‐Itoh, Kyoko; Tsukihara, Tomitake

doi:10.1107/s0907444905023358

Cited by 9 publications

(4 citation statements)

References 23 publications

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“…The absolute stereochemistry is unknown, and may not be determined for free CV‐bilin in solution, as this chiral center is susceptible to racemization, as shown for heme A . In its natural complex with cytochrome c oxidase, however, the absolute configuration has been shown to be S by X‐ray structure analysis . By analogy with heme A, the overall conformation of CV‐bilin and the stereochemistry at C‐1′ are thought to be determined by interaction with the protein.…”

Section: Discussionmentioning

confidence: 99%

Structure of a novel farnesylated bilin from an insect – formation by α‐cleavage of heme A of mitochondrial cytochrome c oxidases?

2014

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Biliproteins are present in almost all forms of life, and many of them play vital roles in photobiology. The bilin ligand of a recently characterized 500‐kDa biliprotein from an insect has been isolated and its structure elucidated with chemical and spectroscopic techniques (UV–visible, IR, MS, NMR, and CD). This blue pigment, named CV‐bilin, represents a unique high molecular mass derivative of biliverdin IXα, with an unusual 10E‐configuration and a molecular mass of 852 Da, corresponding to C48H60N4O10. The high mass of this open‐chain tetrapyrrole results from the presence of an epoxi‐dihydroxyethylfarnesyl substituent at C‐18 and a hydroxymethyl substituent at C‐13. This substitution pattern exactly reflects that of heme A of mitochondrial cytochrome c oxidases with a hydroxyethylfarnesyl chain and a formyl group at corresponding positions of the cyclic tetrapyrrole. As no other natural product is known to show these structural features (heme O, the precursor of heme A, has a methyl group at C‐13), this bilin is presumed to be derived from heme A by cleavage of the α‐methine bridge and oxidative modifications at C‐13 and the hydroxyethylfarnesyl chain. Possibly, a bilin structurally related to this insect bilin is also produced in other organisms as a result of mitochondrial turnover or degradation. As CV‐bilin in complex with a specific protein is accumulated at the end of larval life, stored in the pupa, and finally transferred to the oocytes, a possible role of the free or protein‐bound pigment in egg or embryonic development is discussed.

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Section: Discussionmentioning

confidence: 99%

Structure of a novel farnesylated bilin from an insect – formation by α‐cleavage of heme A of mitochondrial cytochrome c oxidases?

2014

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“…Crystallization or organic synthesis of heme A has never been successfully conducted in the context of the structural analysis. Instead, in 2005, 30 years after the initial report of the heme A structure, a newly developed method was applied to the X-ray structure at 1.8 Å resolution; the results determined that the chiral center is in the S -configuration. As shown in Figure , both hemes are fixed in essentially perpendicular orientations relative to the plane of the mitochondrial membrane.…”

Section: Structure Of Ccomentioning

confidence: 99%

Reaction Mechanism of Cytochrome c Oxidase

2015

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Figure 11. Overall structure of bo 3 CcO of E. coli. Subunits I, II, III, and IV are yellow-green, green, blue, and pink, respectively. Hemes b and o 3 are shown as red and light blue structures. Views along the membrane normal from the periplasmic side (top) and parallel to the membrane (bottom) are given. The dotted circles denote the possible ubiquinolbinding site. It should be noted that the extramabrane domain of subunit II does not have any metal site. Reprinted with permission from ref 45.

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“…Since heme A is quite unstable compared to heme B and has a significantly more complex structure, its molecular structure was determined as late as 1975, except for the absolute configuration of the asymmetric carbon of the hydroxyfarnesylethyl group [15]. This was determined to be an S-conformation in 2005 by X-ray structural analyses [16]. The two hemes A interact with the protein moiety (subunit I) in different ways to provide completely different functions.…”

Section: Structure and Stoichiometry Of The Metal Sitesmentioning

confidence: 99%

Respiratory Conservation of Energy with Dioxygen: Cytochrome c Oxidase

Shimada¹,

Shinzawa‐Itoh²

2014

Sustaining Life on Planet Earth: Metalloenzymes Mastering Dioxygen and Other Chewy Gases

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Cytochrome c oxidase (CcO) is the terminal oxidase of cell respiration which reduces molecular oxygen (O₂) to H2O coupled with the proton pump. For elucidation of the mechanism of CcO, the three-dimensional location and chemical reactivity of each atom composing the functional sites have been extensively studied by various techniques, such as crystallography, vibrational and time-resolved electronic spectroscopy, since the X-ray structures (2.8 Å resolution) of bovine and bacterial CcO have been published in 1995.X-ray structures of bovine CcO in different oxidation and ligand binding states showed that the O₂reduction site, which is composed of Fe (heme a 3) and Cu (CuB), drives a non-sequential four-electron transfer for reduction of O₂to water without releasing any reactive oxygen species. These data provide the crucial structural basis to solve a long-standing problem, the mechanism of the O₂reduction.Time-resolved resonance Raman and charge translocation analyses revealed the mechanism for coupling between O₂reduction and the proton pump: O₂is received by the O₂reduction site where both metals are in the reduced state (R-intermediate), giving the O₂-bound form (A-intermediate). This is spontaneously converted to the P-intermediate, with the bound O₂fully reduced to 2 O²⁻. Hereafter the P-intermediate receives four electron equivalents from the second Fe site (heme a), one at a time, to form the three intermediates, F, O, and E to regenerate the R-intermediate. Each electron transfer step from heme a to the O₂reduction site is coupled with the proton pump.X-ray structural and mutational analyses of bovine CcO show three possible proton transfer pathways which can transfer pump protons (H) and chemical (water-forming) protons (K and D). The structure of the H-pathway of bovine CcO indicates that the driving force of the proton pump is the electrostatic repulsion between the protons on the H-pathway and positive charges of heme a, created upon oxidation to donate electrons to the O₂reduction site. On the other hand, mutational and time-resolved electrometric findings for the bacterial CcO strongly suggest that the D-pathway transfers both pump and chemical protons. However, the structure for the proton-gating system in the D-pathway has not been experimentally identified. The structural and functional diversities in CcO from various species suggest a basic proton pumping mechanism in which heme a pumps protons while heme a 3 reduces O₂as proposed in 1978.

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Absolute configuration of the hydroxyfarnesylethyl group of haem A, determined by X-ray structural analysis of bovine heart cytochromecoxidase using methods applicable at 2.8 Å resolution

Cited by 9 publications

References 23 publications

Structure of a novel farnesylated bilin from an insect – formation by α‐cleavage of heme A of mitochondrial cytochrome c oxidases?

Structure of a novel farnesylated bilin from an insect – formation by α‐cleavage of heme A of mitochondrial cytochrome c oxidases?

Reaction Mechanism of Cytochrome c Oxidase

Respiratory Conservation of Energy with Dioxygen: Cytochrome c Oxidase

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