%0 Journal Article %1 Langley2000OTCasePhaseolotoxin %A Langley, David B. %A Templeton, Matthew D. %A Fields, Barry A. %A Mitchell, Robin E. %A Collyer, Charles A. %D 2000 %J Journal of Biological Chemistry %K OTCase ornithine phaseolotoxin %N 26 %P 20012-20019 %R 10.1074/jbc.M000585200 %T Mechanism of Inactivation of Ornithine Transcarbamoylase by N δ-(N′-Sulfodiaminophosphinyl)-l-ornithine, a True Transition State Analogue?: CRYSTAL STRUCTURE AND IMPLICATIONS FOR CATALYTIC MECHANISM %U http://www.jbc.org/content/275/26/20012.abstract %V 275 %X The crystal structure is reported at 1.8 Å resolution of Escherichia coli ornithine transcarbamoylase in complex with the active derivative of phaseolotoxin fromPseudomonas syringae pv. phaseolicola,N δ-(N′-sulfodiaminophosphinyl)-l-ornithine. Electron density reveals that the complex is not a covalent adduct as previously thought. Kinetic data confirm thatN δ-(N′-sulfodiaminophosphinyl)-l-ornithine exhibits reversible inhibition with a half-life in the order of ∼22 h and a dissociation constant of K D = 1.6 × 10−12 m at 37 °C and pH 8.0. Observed hydrogen bonding about the chiral tetrahedral phosphorus of the inhibitor is consistent only with the presence of the R enantiomer. A strong interaction is also observed between Arg57 Nε and the P-N-S bridging nitrogen indicating that imino tautomers ofN δ-(N′-sulfodiaminophosphinyl)-l-ornithine are present in the bound state. An imino tautomer ofN δ-(N′-sulfodiaminophosphinyl)-l-ornithine is structurally analogous to the proposed reaction transition state. Hence, we propose thatN δ-(N′-sulfodiaminophosphinyl)-l-ornithine, with its three unique N-P bonds, represents a true transition state analogue for ornithine transcarbamoylases, consistent with the tight binding kinetics observed.

@article{Langley2000OTCasePhaseolotoxin, abstract = {The crystal structure is reported at 1.8 Å resolution of Escherichia coli ornithine transcarbamoylase in complex with the active derivative of phaseolotoxin fromPseudomonas syringae pv. phaseolicola,N δ-(N′-sulfodiaminophosphinyl)-l-ornithine. Electron density reveals that the complex is not a covalent adduct as previously thought. Kinetic data confirm thatN δ-(N′-sulfodiaminophosphinyl)-l-ornithine exhibits reversible inhibition with a half-life in the order of ∼22 h and a dissociation constant of K D = 1.6 × 10−12 m at 37 °C and pH 8.0. Observed hydrogen bonding about the chiral tetrahedral phosphorus of the inhibitor is consistent only with the presence of the R enantiomer. A strong interaction is also observed between Arg57 Nε and the P-N-S bridging nitrogen indicating that imino tautomers ofN δ-(N′-sulfodiaminophosphinyl)-l-ornithine are present in the bound state. An imino tautomer ofN δ-(N′-sulfodiaminophosphinyl)-l-ornithine is structurally analogous to the proposed reaction transition state. Hence, we propose thatN δ-(N′-sulfodiaminophosphinyl)-l-ornithine, with its three unique N-P bonds, represents a true transition state analogue for ornithine transcarbamoylases, consistent with the tight binding kinetics observed.}, added-at = {2016-08-11T17:44:18.000+0200}, author = {Langley, David B. and Templeton, Matthew D. and Fields, Barry A. and Mitchell, Robin E. and Collyer, Charles A.}, biburl = {https://www.bibsonomy.org/bibtex/245f761967796a7dcd81f0ff899d71936/salotz}, description = {Mechanism of Inactivation of Ornithine Transcarbamoylase by N δ-(N′-Sulfodiaminophosphinyl)-l-ornithine, a True Transition State Analogue?}, doi = {10.1074/jbc.M000585200}, eprint = {http://www.jbc.org/content/275/26/20012.full.pdf+html}, interhash = {9b1a1559a5c1bc0b1580a15a483b7468}, intrahash = {45f761967796a7dcd81f0ff899d71936}, journal = {Journal of Biological Chemistry}, keywords = {OTCase ornithine phaseolotoxin}, number = 26, pages = {20012-20019}, timestamp = {2016-08-11T17:44:18.000+0200}, title = {Mechanism of Inactivation of Ornithine Transcarbamoylase by N δ-(N′-Sulfodiaminophosphinyl)-l-ornithine, a True Transition State Analogue?: CRYSTAL STRUCTURE AND IMPLICATIONS FOR CATALYTIC MECHANISM}, url = {http://www.jbc.org/content/275/26/20012.abstract}, volume = 275, year = 2000 }