1DUV

CRYSTAL STRUCTURE OF E. COLI ORNITHINE TRANSCARBAMOYLASE COMPLEXED WITH NDELTA-L-ORNITHINE-DIAMINOPHOSPHINYL-N-SULPHONIC ACID (PSORN)

Summary for 1DUV

• Entry DOI: 10.2210/pdb1duv/pdb
• Related: 1OTH 2OTC
• Descriptor: ORNITHINE TRANSCARBAMOYLASE, NDELTA-(N'-SULPHODIAMINOPHOSPHINYL)-L-ORNITHINE, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• Functional Keywords: enzyme-inhibitor complex, transferase
• Biological source: Escherichia coli
• Cellular location: Cytoplasm (Probable): P04391
• Total number of polymer chains: 3
• Total formula weight: 111445.40

Authors

Langley, D.B.,Templeton, M.D.,Fields, B.A.,Mitchell, R.E.,Collyer, C.A. (deposition date: 2000-01-18, release date: 2000-07-04, Last modification date: 2024-02-07)

Primary citation

Langley, D.B.,Templeton, M.D.,Fields, B.A.,Mitchell, R.E.,Collyer, C.A.
Mechanism of inactivation of ornithine transcarbamoylase by Ndelta -(N'-Sulfodiaminophosphinyl)-L-ornithine, a true transition state analogue? Crystal structure and implications for catalytic mechanism.
J.Biol.Chem., 275:20012-20019, 2000

PubMed Abstract: The crystal structure is reported at 1.8 A resolution of Escherichia coli ornithine transcarbamoylase in complex with the active derivative of phaseolotoxin from Pseudomonas syringae pv. phaseolicola, N(delta)-(N'-sulfodiaminophosphinyl)-l-ornithine. Electron density reveals that the complex is not a covalent adduct as previously thought. Kinetic data confirm that N(delta)-(N'-sulfodiaminophosphinyl)-l-ornithine exhibits reversible inhibition with a half-life in the order of approximately 22 h and a dissociation constant of K(D) = 1.6 x 10(-12) m at 37 degrees 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 Arg(57) Nepsilon and the P-N-S bridging nitrogen indicating that imino tautomers of N(delta)-(N'-sulfodiaminophosphinyl)-l-ornithine are present in the bound state. An imino tautomer of N(delta)-(N'-sulfodiaminophosphinyl)-l-ornithine is structurally analogous to the proposed reaction transition state. Hence, we propose that N(delta)-(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.

PubMed: 10747936
DOI: 10.1074/jbc.M000585200

Experimental method

X-RAY DIFFRACTION (1.7 Å)