3bl6
From Proteopedia
Crystal structure of Staphylococcus aureus 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase in complex with formycin A
Overview
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.
About this Structure
3BL6 is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.
Reference
Structure of Staphylococcus aureus 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase., Siu KK, Lee JE, Smith GD, Horvatin-Mrakovcic C, Howell PL, Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 May 1;64(Pt, 5):343-50. Epub 2008 Apr 30. PMID:18453700 Page seeded by OCA on Wed Jun 11 10:47:27 2008
