3dp9 | pdb_00003dp9

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

spinqualitylabelsall models 3dp9, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3dp9 is a 2 chain structure with sequence from "bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BIG, IOD Activity: Adenosylhomocysteine nucleosidase, with EC number 3.2.2.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MTNN_VIBCH] Catalyzes the irreversible cleavage of the glycosidic bond in both 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH/AdoHcy) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively.[HAMAP-Rule:MF_01684] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing.,Gutierrez JA, Crowder T, Rinaldo-Matthis A, Ho MC, Almo SC, Schramm VL Nat Chem Biol. 2009 Apr;5(4):251-7. Epub 2009 Mar 8. PMID:19270684 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA