1duv: Difference between revisions

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

OverviewOverview

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.

About this StructureAbout this Structure

1DUV is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Ornithine carbamoyltransferase, with EC number 2.1.3.3 Full crystallographic information is available from OCA.

ReferenceReference

Mechanism of inactivation of ornithine transcarbamoylase by Ndelta -(N'-Sulfodiaminophosphinyl)-L-ornithine, a true transition state analogue? Crystal structure and implications for catalytic mechanism., Langley DB, Templeton MD, Fields BA, Mitchell RE, Collyer CA, J Biol Chem. 2000 Jun 30;275(26):20012-9. PMID:10747936

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OCA

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-[[Image:1duv.jpg|left|200px]]<br /><applet load="1duv" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1duv.jpg|left|200px]]<br /><applet load="1duv" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1duv, resolution 1.7&Aring;" />
 '''CRYSTAL STRUCTURE OF E. COLI ORNITHINE TRANSCARBAMOYLASE COMPLEXED WITH NDELTA-L-ORNITHINE-DIAMINOPHOSPHINYL-N-SULPHONIC ACID (PSORN)'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-DUV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PSQ and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ornithine_carbamoyltransferase Ornithine carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.3 2.1.3.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1DUV OCA].
+DUV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=PSQ:'>PSQ</scene> and <scene name='pdbligand=MPD:'>MPD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ornithine_carbamoyltransferase Ornithine carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.3 2.1.3.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DUV OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Ornithine carbamoyltransferase]]
 [[Category: Single protein]]
-[[Category: Collyer, C.A.]]
+[[Category: Collyer, C A.]]
-[[Category: Fields, B.A.]]
+[[Category: Fields, B A.]]
-[[Category: Langley, D.B.]]
+[[Category: Langley, D B.]]
-[[Category: Mitchell, R.E.]]
+[[Category: Mitchell, R E.]]
-[[Category: Templeton, M.D.]]
+[[Category: Templeton, M D.]]
 [[Category: MPD]]
 [[Category: PSQ]]
 [[Category: enzyme-inhibitor complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:36:16 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:20:50 2008''