Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase.

Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase. Abstract Text:

Ryosuke Asai,Tomoko Nishino,Tomohiro Matsumura,Ken Okamoto,Kiyohiko Igarashi,Emil F Pai,Takeshi Nishino,Ryosuke Asai,Tomoko Nishino,Tomohiro Matsumura,Ken Okamoto,Kiyohiko Igarashi,Emil F Pai,Takeshi Nishino,

Reactive oxygen species are generated by various systems, including NADPH oxidases, xanthine oxidoreductase (XOR) and mitochondrial respiratory enzymes, and contribute to many physiological and pathological phenomena. Mammalian xanthine dehydrogenase (XDH) can be converted to xanthine oxidase (XO), which produces both superoxide anion and hydrogen peroxide in a molar ratio of about 1:3, depending upon the conditions. Here, we present a mutant of rat XOR that displays mainly XO activity with a superoxide:hydrogen peroxide production ratio of about 6:1. In the mutant, tryptophan 335, which is a component of the amino acid cluster crucial for switching from the XDH to the XO conformation, was replaced with alanine, and phenylalanine 336, which modulates FAD's redox potential through stacking interactions with the flavin cofactor, was changed to leucine. When the mutant was expressed in Sf9 cells, it was obtained in the XO form, and dithiothreitol treatment only partially restored the pyridine nucleotide-binding capacity. The crystal structure of the dithiothreitol-treated mutant at 2.3 Angstroms resolution showed the enzyme's two subunits to be quite similar, but not identical: the cluster involved in conformation-switching was completely disrupted in one subunit, but remained partly associated in the other one. The chain trace of the active site loop in this mutant is very similar to that of the bovine XO form. These results are consistent with the idea that the XDH and XO forms of the mutant are in an equilibrium that greatly favours the XO form, but the equilibrium is partly shifted towards the XDH form upon incubation with dithiothreitol.

Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase. Publishing Authors By Initials

R Asai,T Nishino,T Matsumura,K Okamoto,K Igarashi,EF Pai,T Nishino,R Asai,T Nishino,T Matsumura,K Okamoto,K Igarashi,EF Pai,T Nishino,

For similar enzymes and coenzymes: enzymes: oxidoreductases: alcohol oxidoreductases: xanthine oxidase research abstracts see: enzymes and coenzymes: enzymes: oxidoreductases: alcohol oxidoreductases: xanthine oxidase research

PUBMED ID PMID:

MEDLINE DATE:

Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biochemistry

VOLUME: 141

Page Numbers: 525-34

Journal Abbreviation:

ISSN: 0021-924X

DAY: 14

MONTH: 02

YEAR: 2007

Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376600

Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase. Keywords Mesh Terms:

KEYWORDS: Xanthine Oxidase

MESH TERMS: metabolism

Chemical & Substance for Abstract: Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase. Information

Substance Name: Xanthine Oxidase

Registry Number: EC 1.17.3.2

Grant and Affiliation Information for Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase.

AFFILIATION: Department of Biochemistry and Department of Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Tokyo, Japan.

Country: Japan

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Biochem (Tokyo)

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase Related Publications

• A Gne knockout mouse expressing human GNE D176V mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy.
• Acceptor specificity of ATP:nucleoside-5'-phosphate pyrophosphotransferase from Streptomyces adephospholyticus. Synthesis of the 3'-pyrophosphates of pyrimidine nucleotides, some oligoribonucleotides, 5'-diphosphonucleosidic coenzymes and mG-5'-ppp-5'-Am.
• Acute effects of zolpidem on daytime alertness, psychomotor and physical performance.
• Anti-tumor-initiating effects of monascin, an azaphilonoid pigment from the extract of Monascus pilosus fermented rice (red-mold rice).
• Autophagy in a mouse model of distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy.
• Biogenesis of cocarboxylase in Escherichia coli. Partial purification and some properties of thiamine monophosphate kinase.
• Clinical and neurobiological aspects of narcolepsy.
• Cloning and nucleotide sequence of the ispA gene responsible for farnesyl diphosphate synthase activity in Escherichia coli.
• Deciphering the molecular basis of the broad substrate specificity of alpha-glucosidase from Bacillus sp. SAM1606.
• Effects of epidermal growth factor on the syntheses of DNA and polyamine in isoproterenol-stimulated murine parotid gland.
• Effects of random mutagenesis in a putative substrate-binding domain of geranylgeranyl diphosphate synthase upon intermediate formation and substrate specificity.
• Human xanthine oxidase changes its substrate specificity to aldehyde oxidase type upon mutation of amino acid residues in the active site: roles of active site residues in binding and activation of purine substrate.
• Identification and characterization of geranylgeraniol kinase and geranylgeranyl phosphate kinase from the Archaebacterium Sulfolobus acidocaldarius.
• Identification of genes affecting lycopene formation in Escherichia coli transformed with carotenoid biosynthetic genes: candidates for early genes in isoprenoid biosynthesis.
• Inhibition of neuronal nitric oxide synthase by phosphatidylinositol 4,5-bisphosphate and phosphatidic acid.
• Ki-energy (life-energy) protects isolated rat liver mitochondria from oxidative injury.
• Localization of calpain 3 in human skeletal muscle and its alteration in limb-girdle muscular dystrophy 2A muscle.
• Lung volume and collapsibility of the passive pharynx in patients with sleep-disordered breathing.
• Minimal model analyzing response of glycine receptors expressed in Xenopus oocyte: inhibition by a lipid hydroperoxide.
• Nodular fasciitis of the nose.
• Protein design of geranyl diphosphate synthase. Structural features that define the product specificities of prenyltransferases.
• Purification and characterization of multiple forms of rat liver xanthine oxidoreductase expressed in baculovirus-insect cell system.
• Recognition of allylic substrates in Sulfolobus acidocaldarius geranylgeranyl diphosphate synthase: analysis using mutated enzymes and artificial allylic substrates.
• Selective proteolysis of cytosolic aspartate aminotransferase by a new microbial protease.
• Signal transmission from the suprachiasmatic nucleus to the pineal gland via the paraventricular nucleus: analysed from arg-vasopressin peptide, rPer2 mRNA and AVP mRNA changes and pineal AA-NAT mRNA after the melatonin injection during light and dark per
• Subcellular localization of fukutin and fukutin-related protein in muscle cells.
• The conversion of xanthine dehydrogenase to xanthine oxidase and the role of the enzyme in reperfusion injury.
• The hypocretin/orexin receptor: therapeutic prospective in sleep disorders.
• The hypothalamic peptidergic system, hypocretin/orexin and vigilance control.
• Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase.