1NC1
Crystal structure of E. coli MTA/AdoHcy nucleosidase complexed with 5'-methylthiotubercidin (MTH)
Summary for 1NC1
| Entry DOI | 10.2210/pdb1nc1/pdb |
| Related | 1JYS |
| Descriptor | MTA/SAH nucleosidase, 2-(4-AMINO-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-METHYLSULFANYLMETHYL-TETRAHYDRO-FURAN-3,4-DIOL (3 entities in total) |
| Functional Keywords | mixed alpha/beta dimer, hydrolase |
| Biological source | Escherichia coli |
| Total number of polymer chains | 2 |
| Total formula weight | 51568.94 |
| Authors | Lee, J.E.,Cornell, K.A.,Riscoe, M.K.,Howell, P.L. (deposition date: 2002-12-04, release date: 2003-11-25, Last modification date: 2023-08-16) |
| Primary citation | Lee, J.E.,Cornell, K.A.,Riscoe, M.K.,Howell, P.L. Structure of Escherichia coli 5'-methylthioadenosine/ S-adenosylhomocysteine nucleosidase inhibitor complexes provide insight into the conformational changes required for substrate binding and catalysis. J.Biol.Chem., 278:8761-8770, 2003 Cited by PubMed Abstract: 5'-Methylthioadenosine/S-adenosylhomocysteine (MTA/AdoHcy) nucleosidase is a key enzyme in a number of critical biological processes in many microbes. This nucleosidase catalyzes the irreversible hydrolysis of the N(9)-C(1') bond of MTA or AdoHcy to form adenine and the corresponding thioribose. The key role of the MTA/AdoHcy nucleosidase in biological methylation, polyamine biosynthesis, methionine recycling, and bacterial quorum sensing has made it an important antimicrobial drug target. The crystal structures of Escherichia coli MTA/AdoHcy nucleosidase complexed with the transition state analog, formycin A (FMA), and the nonhydrolyzable substrate analog, 5'-methylthiotubercidin (MTT) have been solved to 2.2- and 2.0-A resolution, respectively. These are the first MTA/AdoHcy nucleosidase structures to be solved in the presence of inhibitors. These structures clearly identify the residues involved in substrate binding and catalysis in the active site. Comparisons of the inhibitor complexes to the adenine-bound MTA/AdoHcy nucleosidase (Lee, J. E., Cornell, K. A., Riscoe, M. K., and Howell, P. L. (2001) Structure (Camb.) 9, 941-953) structure provide evidence for a ligand-induced conformational change in the active site and the substrate preference of the enzyme. The enzymatic mechanism has been re-examined. PubMed: 12496243DOI: 10.1074/jbc.M210836200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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