Structure ofStaphylococcus aureus5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase
| Autor: | Karen K. W. Siu, Jeffrey E. Lee, G. David Smith, P. Lynne Howell, Cathy Horvatin-Mrakovcic |
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| Rok vydání: | 2008 |
| Předmět: |
Staphylococcus aureus
Protein Conformation Stereochemistry Molecular Sequence Data Biophysics medicine.disease_cause Biochemistry Catalysis Protein structure Structural Biology Hydrolase Escherichia coli Genetics medicine Protein Structure Communications Amino Acid Sequence Enzyme Inhibitors Binding site N-Glycosyl Hydrolases chemistry.chemical_classification Binding Sites Thionucleosides Deoxyadenosines Sequence Homology Amino Acid biology Active site Hydrogen Bonding Glycosidic bond Condensed Matter Physics S-Adenosylhomocysteine Kinetics Quorum sensing Enzyme chemistry Drug Design biology.protein Crystallization Formycins Protein Binding |
| Zdroj: | Acta Crystallographica Section F Structural Biology and Crystallization Communications. 64:343-350 |
| ISSN: | 1744-3091 |
| DOI: | 10.1107/s1744309108009275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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