3BL6
Crystal structure of Staphylococcus aureus 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase in complex with formycin A
Summary for 3BL6
| Entry DOI | 10.2210/pdb3bl6/pdb |
| Related | 1NC3 2QTT |
| Descriptor | 5'-methylthioadenosine nucleosidase/S-adenosylhomocysteine nucleosidase, (1S)-1-(7-amino-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1,4-anhydro-D-ribitol (3 entities in total) |
| Functional Keywords | nucleosidase, mtan, alpha and beta proteins, hydrolase |
| Biological source | Staphylococcus aureus |
| Total number of polymer chains | 1 |
| Total formula weight | 25023.58 |
| Authors | Siu, K.K.W.,Lee, J.E.,Smith, G.D.,Horvatin, C.,Howell, P.L. (deposition date: 2007-12-10, release date: 2008-06-10, Last modification date: 2024-02-21) |
| Primary citation | Siu, K.K.,Lee, J.E.,Smith, G.D.,Horvatin-Mrakovcic, C.,Howell, P.L. Structure of Staphylococcus aureus 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase Acta Crystallogr.,Sect.F, 64:343-350, 2008 Cited by PubMed Abstract: 5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) and plays a key role in four metabolic processes: biological methylation, polyamine biosynthesis, methionine recycling and bacterial quorum sensing. The absence of the nucleosidase in mammalian species has implicated this enzyme as a target for antimicrobial drug design. MTAN from the pathogenic bacterium Staphylococcus aureus (SaMTAN) has been kinetically characterized and its structure has been determined in complex with the transition-state analogue formycin A (FMA) at 1.7 A resolution. A comparison of the SaMTAN-FMA complex with available Escherichia coli MTAN structures shows strong conservation of the overall structure and in particular of the active site. The presence of an extra water molecule, which forms a hydrogen bond to the O4' atom of formycin A in the active site of SaMTAN, produces electron withdrawal from the ribosyl group and may explain the lower catalytic efficiency that SaMTAN exhibits when metabolizing MTA and SAH relative to the E. coli enzyme. The implications of this structure for broad-based antibiotic design are discussed. PubMed: 18453700DOI: 10.1107/S1744309108009275 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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