3DF9

Crystal structure of E. coli MTA/SAH nucleosidase in complex with BnT-DADMeImmA

Summary for 3DF9

• Entry DOI: 10.2210/pdb3df9/pdb
• Related: 1Y6Q 1Y6R
• Descriptor: MTA/SAH nucleosidase, (3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[(benzylsulfanyl)methyl]pyrrolidin-3-ol (3 entities in total)
• Functional Keywords: mixed alpha/beta dimer, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 51715.21

Authors

Siu, K.K.W.,Howell, P.L. (deposition date: 2008-06-11, release date: 2009-03-17, Last modification date: 2023-08-30)

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

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: 18453700
DOI: 10.1107/S1744309108009275

Experimental method

X-RAY DIFFRACTION (1.95 Å)