The effect of conformational variability of phosphotriesterase upon N-acyl-L-homoserine lactone and paraoxon binding: insights from molecular dynamics studies

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Dongling ZhanWeiwei Han

Abstract

The organophosphorous hydrolase (PTE) from Brevundimonas diminuta is capable of degrading extremely toxic organophosphorous compounds with a high catalytic turnover and broad substrate specificity. Although the natural substrate for PTE is unknown, its loop remodeling (loop 7-2/H254R) led to the emergence of a homoserine lactonase (HSL) activity that is undetectable in PTE (kcat/km values of up to 2 × 10(4)), with only a minor decrease in PTE paraoxonase activity. In this study, homology modeling and molecular dynamics simulations have been undertaken seeking to explain the reason for the substrate specificity for the wild-type and the loop 7-2/H254R variant. The cavity volume estimated results showed that the active pocket of the variant was almost two fold larger than that of the wild-type (WT) enzyme. pKa calculations for the enzyme (the WT and the variant) showed a significant pKa shift from WT standard values (ΔpKa = 3.5 units) for the His254 residue (in the Arg254 variant). Molecular dynamics simulations indicated that the displacement of loops 6 and 7 over the active site in loop 7-2/H254R variant is useful for N-acyl-L-homoserine lactone (C4-HSL) with a large aliphatic chain to site in the channels easily. Thence the ex...Continue Reading

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Citations

Feb 12, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dongling ZhanWeiwei Han
May 2, 2015·Journal of Biomolecular Structure & Dynamics·Dongling ZhanSong Wang

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Methods Mentioned

BETA
X-ray

Software Mentioned

propKa
Discovery Studio
CASTp
Pymol
_ 3D
QMEAN
Errat
GROMACS
GROMOS
Procheck

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