1EYW

THREE-DIMENSIONAL STRUCTURE OF THE ZINC-CONTAINING PHOSPHOTRIESTERASE WITH BOUND SUBSTRATE ANALOG TRIETHYLPHOSPHATE

Summary for 1EYW

• Entry DOI: 10.2210/pdb1eyw/pdb
• Related: 1EZ2
• Descriptor: PHOSPHOTRIESTERASE, ZINC ION, TRIETHYL PHOSPHATE, ... (5 entities in total)
• Functional Keywords: hydrolase, organophosphate, zinc
• Biological source: Brevundimonas diminuta
• Cellular location: Cell membrane; Peripheral membrane protein: P0A434
• Total number of polymer chains: 1
• Total formula weight: 36395.10

Authors

Holden, H.M.,Benning, M.M.,Raushel, F.M.,Hong, S.-B. (deposition date: 2000-05-09, release date: 2000-12-20, Last modification date: 2017-10-04)

Primary citation

Benning, M.M.,Hong, S.B.,Raushel, F.M.,Holden, H.M.
The binding of substrate analogs to phosphotriesterase.
J.Biol.Chem., 275:30556-30560, 2000

PubMed Abstract: Phosphotriesterase (PTE) from Pseudomonas diminuta catalyzes the detoxification of organophosphates such as the widely utilized insecticide paraoxon and the chemical warfare agent sarin. The three-dimensional structure of the enzyme is known from high resolution x-ray crystallographic analyses. Each subunit of the homodimer folds into a so-called TIM barrel, with eight strands of parallel beta-sheet. The two zinc ions required for activity are positioned at the C-terminal portion of the beta-barrel. Here, we describe the three-dimensional structure of PTE complexed with the inhibitor diisopropyl methyl phosphonate, which serves as a mimic for sarin. Additionally, the structure of the enzyme complexed with triethyl phosphate is also presented. In the case of the PTE-diisopropyl methyl phosphonate complex, the phosphoryl oxygen of the inhibitor coordinates to the more solvent-exposed zinc ion (2.5 A), thereby lending support to the presumed catalytic mechanism involving metal coordination of the substrate. In the PTE-triethyl phosphate complex, the phosphoryl oxygen of the inhibitor is positioned at 3.4 A from the more solvent-exposed zinc ion. The two structures described in this report provide additional molecular understanding for the ability of this remarkable enzyme to hydrolyze such a wide range of organophosphorus substrates.

PubMed: 10871616
DOI: 10.1074/jbc.M003852200

Experimental method

X-RAY DIFFRACTION (1.9 Å)