1dpm

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(New page: 200px<br /><applet load="1dpm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dpm, resolution 2.1&Aring;" /> '''THREE-DIMENSIONAL STR...)
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'''THREE-DIMENSIONAL STRUCTURE OF THE ZINC-CONTAINING PHOSPHOTRIESTERASE WITH BOUND SUBSTRATE ANALOG DIETHYL 4-METHYLBENZYLPHOSPHONATE'''<br />
'''THREE-DIMENSIONAL STRUCTURE OF THE ZINC-CONTAINING PHOSPHOTRIESTERASE WITH BOUND SUBSTRATE ANALOG DIETHYL 4-METHYLBENZYLPHOSPHONATE'''<br />
==Overview==
==Overview==
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Phosphotriesterase from Pseudomonas diminuta catalyzes the hydrolysis of, paraoxon and related acetylcholinesterase inhibitors with rate, enhancements that approach 10(12). The enzyme requires a binuclear metal, center for activity and as isolated contains 2 equiv of zinc per subunit., Here we describe the three-dimensional structure of the, Zn2+/Zn2+-substituted enzyme complexed with the substrate analog diethyl, 4-methylbenzylphosphonate. Crystals employed in the investigation belonged, to the space group C2 with unit cell dimensions of a = 129.6 A, b = 91.4, A, c = 69.4 A, beta = 91.9 degrees, and two subunits in the asymmetric, unit. The model was refined by least-squares analysis to a nominal, resolution of 2.1 A and a crystallographic R-factor of 15.4% for all, measured X-ray data. As in the previously reported structure of the, cadmium-containing enzyme, the bridging ligands are a carbamylated lysine, residue (Lys 169) and a hydroxide. The zinc ions are separated by 3.3 A., The more buried zinc ion is surrounded by His 55, His 57, Lys 169, Asp, 301, and the bridging hydroxide in a trigonal bipyramidal arrangement as, described for the cadmium-substituted enzyme. Unlike the octahedral, coordination observed for the more solvent-exposed cadmium ion, however, the second zinc is tetrahedrally ligated to Lys 169, His 201, His 230, and, the bridging hydroxide. The diethyl 4-methylbenzylphosphonate occupies a, site near the binuclear metal center with the phosphoryl oxygen of the, substrate analog situated at 3.5 A from the more solvent-exposed zinc ion., The aromatic portion of the inhibitor binds in a fairly hydrophobic, pocket. A striking feature of the active site pocket is the lack of direct, electrostatic interactions between the inhibitor and the protein. This, most likely explains the broad substrate specificity exhibited by, phosphotriesterase. The position of the inhibitor within the active site, suggests that the nucleophile for the hydrolysis reaction is the, metal-bound hydroxide.
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Phosphotriesterase from Pseudomonas diminuta catalyzes the hydrolysis of paraoxon and related acetylcholinesterase inhibitors with rate enhancements that approach 10(12). The enzyme requires a binuclear metal center for activity and as isolated contains 2 equiv of zinc per subunit. Here we describe the three-dimensional structure of the Zn2+/Zn2+-substituted enzyme complexed with the substrate analog diethyl 4-methylbenzylphosphonate. Crystals employed in the investigation belonged to the space group C2 with unit cell dimensions of a = 129.6 A, b = 91.4 A, c = 69.4 A, beta = 91.9 degrees, and two subunits in the asymmetric unit. The model was refined by least-squares analysis to a nominal resolution of 2.1 A and a crystallographic R-factor of 15.4% for all measured X-ray data. As in the previously reported structure of the cadmium-containing enzyme, the bridging ligands are a carbamylated lysine residue (Lys 169) and a hydroxide. The zinc ions are separated by 3.3 A. The more buried zinc ion is surrounded by His 55, His 57, Lys 169, Asp 301, and the bridging hydroxide in a trigonal bipyramidal arrangement as described for the cadmium-substituted enzyme. Unlike the octahedral coordination observed for the more solvent-exposed cadmium ion, however, the second zinc is tetrahedrally ligated to Lys 169, His 201, His 230, and the bridging hydroxide. The diethyl 4-methylbenzylphosphonate occupies a site near the binuclear metal center with the phosphoryl oxygen of the substrate analog situated at 3.5 A from the more solvent-exposed zinc ion. The aromatic portion of the inhibitor binds in a fairly hydrophobic pocket. A striking feature of the active site pocket is the lack of direct electrostatic interactions between the inhibitor and the protein. This most likely explains the broad substrate specificity exhibited by phosphotriesterase. The position of the inhibitor within the active site suggests that the nucleophile for the hydrolysis reaction is the metal-bound hydroxide.
==About this Structure==
==About this Structure==
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1DPM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Brevundimonas_diminuta Brevundimonas diminuta] with ZN, EBP and FMT as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1DPM OCA].
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1DPM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Brevundimonas_diminuta Brevundimonas diminuta] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=EBP:'>EBP</scene> and <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DPM OCA].
==Reference==
==Reference==
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[[Category: Brevundimonas diminuta]]
[[Category: Brevundimonas diminuta]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Benning, M.M.]]
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[[Category: Benning, M M.]]
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[[Category: Holden, H.M.]]
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[[Category: Holden, H M.]]
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[[Category: Raushel, F.M.]]
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[[Category: Raushel, F M.]]
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[[Category: Vanhooke, J.L.]]
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[[Category: Vanhooke, J L.]]
[[Category: EBP]]
[[Category: EBP]]
[[Category: FMT]]
[[Category: FMT]]
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[[Category: zinc]]
[[Category: zinc]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:28:37 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:19:12 2008''

Revision as of 10:19, 21 February 2008

Image:1dpm.gif

1dpm, resolution 2.1Å

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THREE-DIMENSIONAL STRUCTURE OF THE ZINC-CONTAINING PHOSPHOTRIESTERASE WITH BOUND SUBSTRATE ANALOG DIETHYL 4-METHYLBENZYLPHOSPHONATE

Overview

Phosphotriesterase from Pseudomonas diminuta catalyzes the hydrolysis of paraoxon and related acetylcholinesterase inhibitors with rate enhancements that approach 10(12). The enzyme requires a binuclear metal center for activity and as isolated contains 2 equiv of zinc per subunit. Here we describe the three-dimensional structure of the Zn2+/Zn2+-substituted enzyme complexed with the substrate analog diethyl 4-methylbenzylphosphonate. Crystals employed in the investigation belonged to the space group C2 with unit cell dimensions of a = 129.6 A, b = 91.4 A, c = 69.4 A, beta = 91.9 degrees, and two subunits in the asymmetric unit. The model was refined by least-squares analysis to a nominal resolution of 2.1 A and a crystallographic R-factor of 15.4% for all measured X-ray data. As in the previously reported structure of the cadmium-containing enzyme, the bridging ligands are a carbamylated lysine residue (Lys 169) and a hydroxide. The zinc ions are separated by 3.3 A. The more buried zinc ion is surrounded by His 55, His 57, Lys 169, Asp 301, and the bridging hydroxide in a trigonal bipyramidal arrangement as described for the cadmium-substituted enzyme. Unlike the octahedral coordination observed for the more solvent-exposed cadmium ion, however, the second zinc is tetrahedrally ligated to Lys 169, His 201, His 230, and the bridging hydroxide. The diethyl 4-methylbenzylphosphonate occupies a site near the binuclear metal center with the phosphoryl oxygen of the substrate analog situated at 3.5 A from the more solvent-exposed zinc ion. The aromatic portion of the inhibitor binds in a fairly hydrophobic pocket. A striking feature of the active site pocket is the lack of direct electrostatic interactions between the inhibitor and the protein. This most likely explains the broad substrate specificity exhibited by phosphotriesterase. The position of the inhibitor within the active site suggests that the nucleophile for the hydrolysis reaction is the metal-bound hydroxide.

About this Structure

1DPM is a Single protein structure of sequence from Brevundimonas diminuta with , and as ligands. Full crystallographic information is available from OCA.

Reference

Three-dimensional structure of the zinc-containing phosphotriesterase with the bound substrate analog diethyl 4-methylbenzylphosphonate., Vanhooke JL, Benning MM, Raushel FM, Holden HM, Biochemistry. 1996 May 14;35(19):6020-5. PMID:8634243

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