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Titolo:
Formation of a protonated trihydrohiopterin radical cation in the first reaction cycle of neuronal and endothelial nitric oxide synthase detected by electron paramagnetic: Resonance spectroscopy
Autore:
Schmidt, PP; Lange, R; Gorren, ACF; Werner, ER; Mayer, B; Andersson, KK;
Indirizzi:
Univ Oslo, Dept Biochem, N-0316 Oslo, Norway Univ Oslo Oslo Norway N-0316 niv Oslo, Dept Biochem, N-0316 Oslo, Norway INSERM, U128, IFR24, F-34293 Montpellier 5, France INSERM Montpellier France 5 , U128, IFR24, F-34293 Montpellier 5, France Graz Tech Univ, Inst Pharmakol & Toxikol, A-8010 Graz, Austria Graz Tech Univ Graz Austria A-8010 makol & Toxikol, A-8010 Graz, Austria Innsbruck Univ, Inst Med Chem & Biochem, A-6020 Innsbruck, Austria Innsbruck Univ Innsbruck Austria A-6020 ochem, A-6020 Innsbruck, Austria
Titolo Testata:
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
fascicolo: 2, volume: 6, anno: 2001,
pagine: 151 - 158
SICI:
0949-8257(200102)6:2<151:FOAPTR>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINO-ACID HYDROXYLASES; BINDING-SITE; OXYGEN ACTIVATION; CRYSTAL-STRUCTURE; LOW-TEMPERATURE; DIMERIC ENZYME; HEME DOMAIN; L-ARGININE; TETRAHYDROBIOPTERIN; CATALYSIS;
Keywords:
nitric oxide synthase; biopterin; heme; oxygen activation; radical;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Andersson, KK Univ Oslo, Dept Biochem, POB 1041, N-0316 Oslo, Norway Univ Oslo POB 1041 Oslo Norway N-0316 , N-0316 Oslo, Norway
Citazione:
P.P. Schmidt et al., "Formation of a protonated trihydrohiopterin radical cation in the first reaction cycle of neuronal and endothelial nitric oxide synthase detected by electron paramagnetic: Resonance spectroscopy", J BIOL I CH, 6(2), 2001, pp. 151-158

Abstract

Nitric oxide synthase (EC 1.14.13.39; NOS) converts L-arginine into NO andL-citrulline in a two-step reaction with NW-hydroxy-L-arginine (NOHLA) as an intermediate. The active site iron in NOS has thiolate axial heme-iron ligation as found in the related monooxygenase cytochrome P450. In NOS, tetrahydrobiopterin (BH4) is an essential cofactor for both steps, but its function is controversial. Previous optical studies of the reaction between reduced NOS with O-2 at -30 degreesC suggested that BH4 may serve as an one-electron donor in the first cycle, implying formation of a trihydrobiopterin radical. We investigated the same reaction under identical conditions with electron paramagnetic resonance spectroscopy. With BH4-containing full-length neuronal NOS we obtained an organic free radical (g-value 2.0042) in thepresence of Arg, and a similar radical was observed with the endothelial NOS oxygenase domain in the presence of Arg and BH4. Without substrate the radical yield was greatly (10x) diminished. Without BH4, or with NOHLA instead of Arg, no radical was observed. With 6-methyltetrahydropterin or 5-methyl-BH4 instead of BH4, radicals with somewhat different spec-tra were formed. On the basis of simulations we assign the signals to trihydropterin radical cations protonated at N5. This is the first study that demonstrates theformation of a protonated trihydrobiopterin radical with the constitutive isoforms of NOS, and the first time the radical was obtained without exogenous BH4. These results offer strong support for redox cycling of BH, in thefirst reaction cycle of NOS catalysis (BH4 <-> BH3.H+).

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Documento generato il 13/07/20 alle ore 07:50:15