Structure of E. coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase reveals similarity to the purine nucleoside phosphorylases

J E LeeP Lynne Howell


5'-methylthioadenosine/S-adenosyl-homocysteine (MTA/AdoHcy) nucleosidase catalyzes the irreversible cleavage of 5'-methylthioadenosine and S-adenosylhomocysteine to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, 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. The crystal structure of E. coli MTA/AdoHcy nucleosidase was determined at 1.90 A 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 alpha 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. Although the sequence of E. coli MTA/AdoHcy nucleosida...Continue Reading


Apr 1, 1992·Proteins·A L MorrisJ Thornton
Nov 5, 1991·Biochemistry·B A HorensteinVern L Schramm
Jul 1, 1990·Acta Crystallographica. Section A, Foundations of Crystallography·A T BrungerJ W Erickson
May 15, 1973·Journal of Molecular Biology·S T Rao, M G Rossmann
Nov 15, 1984·Biochemical Pharmacology·Michael K RiscoeA J Ferro
Nov 1, 1995·Antimicrobial Agents and Chemotherapy·Janice R SufrinC J Bacchi
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Feb 1, 1996·Protein Science : a Publication of the Protein Society·E G Hutchinson, J Thornton
Oct 8, 1997·Biochemistry·M D ErionSteven E Ealick
Mar 28, 1998·Trends in Biochemical Sciences·D WestheadJ Thornton
Apr 22, 1999·Protein Science : a Publication of the Protein Society·D WestheadJ Thornton
May 13, 1999·Bioinformatics·D GilbertJ Thornton
Sep 18, 1999·Acta Crystallographica. Section D, Biological Crystallography·R W Grosse-Kunstleve, A T Brunger
Oct 26, 1999·Acta Crystallographica. Section D, Biological Crystallography·J W Pflugrath
Apr 28, 2001·Cell Biochemistry and Biophysics·M A TurnerP Lynne Howell
Oct 1, 1989·Parasitology Today·Michael K RiscoeJ H Fitchen


Nov 1, 2003·Bioorganic & Medicinal Chemistry Letters·Gang ZhaoZhaohui Sunny Zhou
Apr 7, 2010·Biochemistry·Debamita PaulSteven E Ealick
Dec 18, 2001·The Biochemical Journal·Matthew J Pugmire, Steven E Ealick
Oct 2, 2003·European Journal of Biochemistry·Tõnu ReintammMerike Kelve
Jul 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·John C WhitneyP Lynne Howell
May 6, 2008·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Karen K W SiuP Lynne Howell
Apr 23, 2004·BMC Microbiology·Agnieszka SekowskaAntoine Danchin
Jan 15, 2014·Acta Crystallographica. Section D, Biological Crystallography·Robbert Q KimKeith A Stubbs
Jul 30, 2014·Nature Nanotechnology·Tanya GordonovWilliam E Bentley
Jun 18, 2010·Journal of Structural Biology·Karen K W SiuP Lynne Howell
Feb 8, 2014·Biochemistry·Shanzhi WangVern L Schramm
Jul 4, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Dustin J LittleP Lynne Howell
Dec 21, 2010·Molecular Microbiology·Nikhat Parveen, Kenneth A Cornell
Aug 23, 2011·Bioorganic & Medicinal Chemistry·Venkata L A MalladiStanislaw F Wnuk
Apr 8, 2015·Acta Crystallographica. Section F, Structural Biology Communications·Yongbin XuNam Chul Ha
Mar 18, 2008·Journal of Molecular Biology·Karen K W SiuP Lynne Howell
Mar 3, 2009·Biochemical and Biophysical Research Communications·Eun Young ParkHyun Kyu Song
Mar 25, 2014·Biochemical and Biophysical Research Communications·Xusheng KangXuejun C Zhang
Jul 6, 2016·Metabolic Engineering·Narendranath BhokishamWilliam E Bentley
Aug 28, 2004·Organic Letters·Joshua F AlfaroZhaohui Sunny Zhou
Mar 1, 2006·Bioorganic & Medicinal Chemistry Letters·Vivekanand P KamathY Sudhakar Babu
Aug 18, 2009·Bioorganic & Medicinal Chemistry·Stanislaw F WnukDehua Pei
Jun 7, 2019·The Journal of Biological Chemistry·François Le MauffDonald C Sheppard
Apr 8, 2020·The FEBS Journal·Sofia S MariasinaVladimir I Polshakov
Jun 20, 2013·The Journal of Biological Chemistry·Laura M RileyP Lynne Howell
Jan 9, 2014·The Journal of Biological Chemistry·Francis WolframP Lynne Howell
Mar 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Lindsey S MarmontP Lynne Howell
Sep 6, 2015·The Journal of Biological Chemistry·Natalie C BamfordDonald C Sheppard
Mar 31, 2015·The Journal of Biological Chemistry·John C WhitneyP Lynne Howell
Mar 30, 2016·The Journal of Biological Chemistry·Matthew McCallumP Lynne Howell
Nov 20, 2016·Proceedings of the National Academy of Sciences of the United States of America·Michael T BancoDonald R Ronning

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