1Z5O

Crystal structure of MTA/AdoHcy nucleosidase Asp197Asn mutant complexed with 5'-methylthioadenosine

Summary for 1Z5O

• Entry DOI: 10.2210/pdb1z5o/pdb
• Related: 1Z5N 1Z5P
• Descriptor: MTA/SAH nucleosidase, 5'-DEOXY-5'-METHYLTHIOADENOSINE (3 entities in total)
• Functional Keywords: mixed alpha/beta, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 51568.94

Authors

Lee, J.E.,Smith, G.D.,Horvatin, C.,Huang, D.J.T.,Cornell, K.A.,Riscoe, M.K.,Howell, P.L. (deposition date: 2005-03-18, release date: 2005-10-04, Last modification date: 2023-08-23)

Primary citation

Lee, J.E.,Smith, G.D.,Horvatin, C.,Huang, D.J.T.,Cornell, K.A.,Riscoe, M.K.,Howell, P.L.
Structural snapshots of MTA/AdoHcy nucleosidase along the reaction coordinate provide insights into enzyme and nucleoside flexibility during catalysis
J.Mol.Biol., 352:559-574, 2005

PubMed Abstract: 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 2.0A, 2.0A, and 2.1A 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.

PubMed: 16109423
DOI: 10.1016/j.jmb.2005.07.027

Experimental method

X-RAY DIFFRACTION (2 Å)