3DF9

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

3DF9 の概要

• エントリーDOI: 10.2210/pdb3df9/pdb
• 関連するPDBエントリー: 1Y6Q 1Y6R
• 分子名称: 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)
• 機能のキーワード: mixed alpha/beta dimer, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51715.21

構造登録者

Siu, K.K.W.,Howell, P.L. (登録日: 2008-06-11, 公開日: 2009-03-17, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.95 Å)