3DP9
Crystal structure of Vibrio cholerae 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with butylthio-DADMe-Immucillin A
Summary for 3DP9
| Entry DOI | 10.2210/pdb3dp9/pdb |
| Descriptor | 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) |
| Functional Keywords | vibrio cholerae 5'-methylthioadenosine/s-adenosyl homocysteine nucleosidase, butylthio dadme immucillin a, mtan, hydrolase |
| Biological source | Vibrio cholerae |
| Total number of polymer chains | 2 |
| Total formula weight | 49888.07 |
| Authors | Ho, M.,Gutierrez, J.A.,Crowder, T.,Rinaldo-Matthis, A.,Almo, S.C.,Schramm, V.L. (deposition date: 2008-07-07, release date: 2009-03-10, Last modification date: 2024-02-21) |
| Primary citation | 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 Cited by 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: 19270684DOI: 10.1038/nchembio.153 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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