4f3c | pdb_00004f3c

Crystal structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Salmonella enterica with butyl-thio-DADMe-Immucillin-A

spinqualitylabelsall models 4f3c, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4f3c is a 2 chain structure with sequence from Salmonella enterica subsp. enterica serovar Choleraesuis str. SCSA50. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BIG, EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Accumulation of 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) in bacteria disrupts the S-adenosylmethionine pool to alter biological methylations, synthesis of polyamines, and production of quorum-sensing molecules. Bacterial metabolism of MTA and SAH depends on MTA/SAH nucleosidase (MTAN), an enzyme not present in humans and a target for quorum sensing because MTAN activity is essential for synthesis of autoinducer-2 molecules. Crystals of Salmonella enterica MTAN with product and transition state analogs of MTA and SAH explain the structural contacts causing pM binding affinity for the inhibitor and reveal a "water-wire" channel for the catalytic nucleophile. The crystal structure shows an extension of the binding pocket filled with polyethylene glycol. We exploited this discovery by the design and synthesis of tailored modifications of the currently existing transition state analogs to fill this site. This site was not anticipated in MTAN structures. Tailored inhibitors with dissociation constants of 5 to 15 pM are characterized. Salmonella enterica MTAN at 1.36 A Resolution: A Structure-Based Design of Tailored Transition State Analogs.,Haapalainen AM, Thomas K, Tyler PC, Evans GB, Almo SC, Schramm VL Structure. 2013 May 14. pii: S0969-2126(13)00121-4. doi:, 10.1016/j.str.2013.04.009. PMID:23685211 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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