7mt4

Crystal structure of tryptophan Synthase in complex with F9, NH4+, pH7.8 - alpha aminoacrylate form - E(A-A)Crystal structure of tryptophan Synthase in complex with F9, NH4+, pH7.8 - alpha aminoacrylate form - E(A-A)

Structural highlights 7mt4 is a 2 chain structure with sequence from Salmonella enterica subsp. enterica serovar Typhimurium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRPA_SALTY The alpha subunit is responsible for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate. Publication Abstract from PubMed NMR-assisted crystallography-the integrated application of solid-state NMR, X-ray crystallography, and first-principles computational chemistry-holds significant promise for mechanistic enzymology: by providing atomic-resolution characterization of stable intermediates in enzyme active sites, including hydrogen atom locations and tautomeric equilibria, NMR crystallography offers insight into both structure and chemical dynamics. Here, this integrated approach is used to characterize the tryptophan synthase alpha-aminoacrylate intermediate, a defining species for pyridoxal-5'-phosphate-dependent enzymes that catalyze beta-elimination and replacement reactions. For this intermediate, NMR-assisted crystallography is able to identify the protonation states of the ionizable sites on the cofactor, substrate, and catalytic side chains as well as the location and orientation of crystallographic waters within the active site. Most notable is the water molecule immediately adjacent to the substrate beta-carbon, which serves as a hydrogen bond donor to the epsilon-amino group of the acid-base catalytic residue betaLys87. From this analysis, a detailed three-dimensional picture of structure and reactivity emerges, highlighting the fate of the L-serine hydroxyl leaving group and the reaction pathway back to the preceding transition state. Reaction of the alpha-aminoacrylate intermediate with benzimidazole, an isostere of the natural substrate indole, shows benzimidazole bound in the active site and poised for, but unable to initiate, the subsequent bond formation step. When modeled into the benzimidazole position, indole is positioned with C3 in contact with the alpha-aminoacrylate C(beta) and aligned for nucleophilic attack. Here, the chemically detailed, three-dimensional structure from NMR-assisted crystallography is key to understanding why benzimidazole does not react, while indole does. Imaging active site chemistry and protonation states: NMR crystallography of the tryptophan synthase alpha-aminoacrylate intermediate.,Holmes JB, Liu V, Caulkins BG, Hilario E, Ghosh RK, Drago VN, Young RP, Romero JA, Gill AD, Bogie PM, Paulino J, Wang X, Riviere G, Bosken YK, Struppe J, Hassan A, Guidoulianov J, Perrone B, Mentink-Vigier F, Chang CA, Long JR, Hooley RJ, Mueser TC, Dunn MF, Mueller LJ Proc Natl Acad Sci U S A. 2022 Jan 11;119(2):e2109235119. doi: , 10.1073/pnas.2109235119. PMID:34996869 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tryptophan synthase 3D structures

spinqualitylabelsall models 7mt4, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image