3DP9

Crystal structure of Vibrio cholerae 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with butylthio-DADMe-Immucillin A

3DP9 の概要

• エントリーDOI: 10.2210/pdb3dp9/pdb
• 分子名称: MTA/SAH nucleosidase, (3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[(butylsulfanyl)methyl]pyrrolidin-3-ol, IODIDE ION, ... (4 entities in total)
• 機能のキーワード: vibrio cholerae 5'-methylthioadenosine/s-adenosyl homocysteine nucleosidase, butylthio dadme immucillin a, mtan, hydrolase
• 由来する生物種: Vibrio cholerae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49888.07

構造登録者

Ho, M.,Gutierrez, J.A.,Crowder, T.,Rinaldo-Matthis, A.,Almo, S.C.,Schramm, V.L. (登録日: 2008-07-07, 公開日: 2009-03-10, 最終更新日: 2024-02-21)

主引用文献

Gutierrez, J.A.,Crowder, T.,Rinaldo-Matthis, A.,Ho, M.C.,Almo, S.C.,Schramm, V.L.
Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing.
Nat.Chem.Biol., 5:251-257, 2009

PubMed Abstract: 5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is a bacterial enzyme involved in S-adenosylmethionine-related quorum sensing pathways that induce bacterial pathogenesis factors. Transition state analogs MT-DADMe-Immucillin-A, EtT-DADMe-Immucillin-A and BuT-DADMe-Immucillin-A are slow-onset, tight-binding inhibitors of Vibrio cholerae MTAN (VcMTAN), with equilibrium dissociation constants of 73, 70 and 208 pM, respectively. Structural analysis of VcMTAN with BuT-DADMe-Immucillin-A revealed interactions contributing to the high affinity. We found that in V. cholerae cells, these compounds are potent MTAN inhibitors with IC(50) values of 27, 31 and 6 nM for MT-, EtT- and BuT-DADMe-Immucillin-A, respectively; the compounds disrupt autoinducer production in a dose-dependent manner without affecting growth. MT- and BuT-DADMe-Immucillin-A also inhibited autoinducer-2 production in enterohemorrhagic Escherichia coli O157:H7 with IC(50) values of 600 and 125 nM, respectively. BuT-DADMe-Immucillin-A inhibition of autoinducer-2 production in both strains persisted for several generations and caused reduction in biofilm formation. These results support MTAN's role in quorum sensing and its potential as a target for bacterial anti-infective drug design.

PubMed: 19270684
DOI: 10.1038/nchembio.153

実験手法

X-RAY DIFFRACTION (2.3 Å)