Structural snapshots of MTA/AdoHcy nucleosidase along the reaction coordinate provide insights into enzyme and nucleoside flexibility during catalysis

Jeffrey E. Lee, G. David Smith, Cathy Horvatin, David J.T. Huang, Kenneth A. Cornell, Michael K. Riscoe, P. Lynne Howell

Research output: Contribution to journalArticle

30 Scopus citations


MTA/AdoHcy nucleosidase (MTAN) irreversibly hydrolyzes the N9-C1′ bond in the nucleosides, 5′-methylthioadenosine (MTA) and S-adenosylhomocysteine (AdoHcy) to form adenine and the corresponding thioribose. MTAN plays a vital role in metabolic pathways involving methionine recycling, biological methylation, polyamine biosynthesis, and quorum sensing. Crystal structures of a wild-type (WT) MTAN complexed with glycerol, and mutant-enzyme and mutant-product complexes have been determined at 2.0 Å, 2.0 Å, and 2.1 Å resolution, respectively. The WT MTAN-glycerol structure provides a purine-free model and in combination with the previously solved thioribose-free MTAN-ADE structure, we now have separate apo structures for both MTAN binding subsites. The purine and thioribose-free states reveal an extensive enzyme-immobilized water network in their respective binding subsites. The Asp197Asn MTAN-MTA and Glu12Gln MTAN-MTR·ADE structures are the first enzyme-substrate and enzyme-product complexes reported for MTAN, respectively. These structures provide representative snapshots along the reaction coordinate and allow insight into the conformational changes of the enzyme and the nucleoside substrate. A "catalytic movie" detailing substrate binding, catalysis, and product release is presented.

Original languageEnglish (US)
Pages (from-to)559-574
Number of pages16
JournalJournal of molecular biology
Issue number3
StatePublished - Sep 23 2005



  • 5′-methylthioadenosine
  • 5′-methylthioadenosine/S- adenosylhomocysteine nucleosidase
  • Conformational flexibility
  • Reaction coordinate
  • S-adenosylhomocysteine

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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