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Titolo:
Structure of E-coli 5 '-methylthioadenosine/S-adenosylhomocysteine nucleosidase reveals similarity to the purine nucleoside phosphorylases
Autore:
Lee, JE; Cornell, KA; Riscoe, MK; Howell, PL;
Indirizzi:
Hosp Sick Children, Struct Biol & Biochem Res Inst, Toronto, ON M5G 1X8, Canada Hosp Sick Children Toronto ON Canada M5G 1X8 Toronto, ON M5G 1X8, Canada Univ Toronto, Fac Med, Dept Biochem, Toronto, ON M6S 1A8, Canada Univ Toronto Toronto ON Canada M6S 1A8 ochem, Toronto, ON M6S 1A8, Canada Portland State Univ, Dept Chem, Portland, OR 97207 USA Portland State Univ Portland OR USA 97207 pt Chem, Portland, OR 97207 USA Vet Affairs Med Ctr, Med Res Serv, Portland, OR 97021 USA Vet Affairs Med Ctr Portland OR USA 97021 es Serv, Portland, OR 97021 USA Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 l Biol, Portland, OR 97201 USA
Titolo Testata:
STRUCTURE
fascicolo: 10, volume: 9, anno: 2001,
pagine: 941 - 953
SICI:
0969-2126(200110)9:10<941:SOE5'N>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESCHERICHIA-COLI; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; CATALYTIC MECHANISM; DIFFRACTION DATA; 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE; 3-DIMENSIONAL STRUCTURE; CRITHIDIA-FASCICULATA; TRANSITION-STATE; TOPOLOGY;
Keywords:
5 '-methylthioadenosine/S-adenosylhomocysteine; nucleosidase; methylthioadenosine phosphorylase; purine nucleoside phosphorylase; methionine recycling pathway; structure-based drug design; enzyme mechanism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Howell, PL Hosp Sick Children, Struct Biol & Biochem Res Inst, 555 Univ Ave, Toronto,ON M5G 1X8, Canada Hosp Sick Children 555 Univ Ave Toronto ON Canada M5G 1X8 anada
Citazione:
J.E. Lee et al., "Structure of E-coli 5 '-methylthioadenosine/S-adenosylhomocysteine nucleosidase reveals similarity to the purine nucleoside phosphorylases", STRUCTURE, 9(10), 2001, pp. 941-953

Abstract

Background: 5'-methylthioadenosine/S-adenosy-homocysteine (MTA/AdoHcy) nucleosidase catalyzes the irreversible cleavage of 5'-methylthioadenosine andS-adenosylhomocysteine to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomo-cysteine, respectively. While this enzyme is crucial for the metabolism of AdoHcy and MTA nucleosides in many prokaryotic and lower eukaryotic organisms, it is absent in mammalian cells. This metabolic difference represents an exploitable target for rational drug design. Results: The crystal structure of E. coli MTA/AdoHcy nucleosidase was determined at 1.90 Angstrom resolution with the multiwavelength anomalous diffraction (MAD) technique. Each monomer of the MTA/AdoHcy nucleosidase dimer consists of a mixed alpha/beta domain with a nine-stranded mixed beta sheet,flanked by six a helices and a small 3(10) helix. Intersubunit contacts between the two monomers present in the asymmetric unit are mediated primarily by helix-helix and helix-loop hydrophobic interactions. The unexpected presence of an adenine molecule in the active site of the enzyme has allowed the identification of both substrate binding and potential catalytic amino acid residues. Conclusions: Although the sequence of E. coli MTA/AdoHcy nucleosidase has almost no identity with any known enzyme, its tertiary structure is similarto both the mammalian (trimeric) and prokaryotic (hexameric) purine nucleoside phosphorylases. The structure provides evidence that this protein is functional as a dimer and that the dual specificity for MTA and AdoHcy results from the truncation of a helix. The structure of MTA/AdoHcy nucleosidaseis the first structure of a prokaryotic nucleoside N-ribohydrolase specific for 6-aminopurines.

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Documento generato il 14/07/20 alle ore 12:39:52