X-ray snapshots of quinone cofactor biogenesis in bacterial copper amine oxidase

Kim, M.; Okajima, Toshihide; Kishishita, S.; Yoshimura, M.; Kawamori, Asako; Tanizawa, Katsuyuki; Yamaguchi, Hiroshi

doi:10.1107/s0108767302096915

Cited by 5 publications

(6 citation statements)

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“…Similar observations were reported in the case of a biomineralized marine shell valve where the proteins involve in biomineralization of the shell surface [20] and also in CaS material [40] containing manganese ions in traces. Such signal at g=1.9983 is in good agreement with those reported for Cr 3+ in biological complex [41]. As is seen in Fig.…”

Section: Discussionsupporting

confidence: 93%

Structural studies of the biomineralized species of calcified pancreatic stones in patients suffering from chronic pancreatitis

Narasimhulu¹,

Gopal²,

Rao³

et al. 2005

Biophysical Chemistry

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Section: Discussionsupporting

confidence: 93%

Structural studies of the biomineralized species of calcified pancreatic stones in patients suffering from chronic pancreatitis

Narasimhulu¹,

Gopal²,

Rao³

et al. 2005

Biophysical Chemistry

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“…It is observed that the generation of PROS decreases by ∼50% in the absence of the Tyr10 residue for all the complexes, demonstrating that Tyr10 is the source of the second electron during PROS formation ( Figure 3B) as observed in several enzyme systems. 34 The transfer of an electron from Tyr10 to O 2 will subsequently lead to the formation of a tyrosyl radical that can cause dimerization of the peptides cross-linked via the tyrosine residue, which are characteristic features of AD. 35 The formation of an Fe−O 2 intermediate ( Figure 3C, blue) is the first step involved in the PROS generation pathway by the Fe(II) center, and this intermediate has been trapped and characterized in numerous heme proteins and their synthetic analogues.…”

Section: •−mentioning

confidence: 99%

Alzheimer’s Disease: A Heme–Aβ Perspective

et al. 2015

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CONSPECTUS: Redox active iron is utilized in biology for various electron transfer and catalytic reactions essential for life, yet this same chemistry mediates the formation of partially reduced oxygen species (PROS). Oxidative stress derived from the iron accumulated in the amyloid plaques originating from amyloid β (Aβ) peptides and neurofibrillary tangles derived from hyperphosphorylated tau proteins has been implicated in the pathogenesis of Alzheimer's disease (AD). Altered heme homeostasis leading to dysregulation of expression of heme proteins and heme deposits in the amyloid plaques are characteristic of the AD brain. However, the pathogenic significance of heme in neurodegeneration in AD has been unappreciated due to the lack of detailed understanding of the chemistry of the interaction of heme and Aβ peptides. As a result, the biochemistry and biophysics of heme complexes of Aβ peptides (heme−Aβ) remained largely unexplored. In this Account, we discuss the active site environment of heme bound Aβ complexes, which involves three amino acid residues unique in mammalian Aβ (Arg5, Tyr10, and His13) and missing in Aβ from rodents, which do not get affected by AD. The histidine residue binds heme, while the arginine and the tyrosine act as key second sphere residues of the heme−Aβ active site that play a crucial role in its reactivity. Generation of PROS, enhanced peroxidase activity, and oxidation of neurotransmitters such as serotonin (5-HT) are all found to be catalyzed by heme−Aβ in in vitro assays, and these reactivities can potentially be linked to the observed neuropathologies in AD brain. Association of Cu with heme−Aβ leads to the formation of heme−Cu−Aβ. The heme−Cu−Aβ complex produces a greater amount of PROS than reduced heme−Aβ or Cu−Aβ alone. Nitric oxide (NO), a signaling molecule, is found to ameliorate the detrimental effects of heme−Aβ and Cu bound heme−Aβ complexes by detaching heme from the heme−Aβ complex and releasing it into the environment solution. Heme−Aβ complexes show fast electron transfer with oxidized cytochrome c and rapid heme transfer with apomyoglobin and aponeuroglobin. NO, cytochrome c, and apoglobins can all lead to reduction in PROS generated by reduced heme−Aβ. Synthetic analogues of heme, offering a hydrophobic distal environment, have been used to trap oxygen bound intermediates, which provides insight into the mechanism of PROS generation by reduced heme−Aβ. Artificial constructs of Aβ on nonbiological platforms are used not only to stabilize metastable and physiologically relevant large and small amyloid aggregates but also to monitor the interaction of various drug candidates with heme and Cu bound Aβ aggregates, representing a tractable avenue for testing therapeutic agents targeting metals and cofactors in AD.

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“…During this maturation process, two molar equivalents of dioxygen are consumed, one incorporated into the TPQ and another reduced to hydrogen peroxide [26]. Several intermediates have been trapped in crystals by controlling the availability of copper and oxygen, as well as the length of time for maturation to occur [27]. Since the mature enzyme has a distinct UV-visible spectrum, crystals can be monitored as a function of time and cryogenically preserved at different points of the maturation process.…”

Section: Amine Oxidasesmentioning

confidence: 99%

Type-2 copper-containing enzymes

Macpherson

Murphy

2007

Cell. Mol. Life Sci.

120

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Type-2 Cu sites are found in all the major branches of life and are often involved in the catalysis of oxygen species. Four type-2 Cu protein families are selected as model systems for review: amine oxidases, Cu monooxygenases, nitrite reductase/multicopper oxidase, and CuZn superoxide dismutase. For each model protein, the availability of multiple crystal structures and detailed enzymological studies provides a detailed molecular view of the type-2 Cu site and delineation of the mechanistic role of the Cu in biological function. Comparison of these model proteins leads to the identification of common properties of the Cu sites and insight into the evolution of the trinuclear active site found in multicopper oxidases.

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X-ray snapshots of quinone cofactor biogenesis in bacterial copper amine oxidase

Cited by 5 publications

References 0 publications

Structural studies of the biomineralized species of calcified pancreatic stones in patients suffering from chronic pancreatitis

Structural studies of the biomineralized species of calcified pancreatic stones in patients suffering from chronic pancreatitis

Alzheimer’s Disease: A Heme–Aβ Perspective

Type-2 copper-containing enzymes

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