Investigating coordination flexibility of glycerophosphodiesterase (GpdQ) through interactions with mono-, di-, and triphosphoester (NPP, BNPP, GPE, and paraoxon) substrates

Abstract

Interactions of the catalytically active binuclear form of glycerophosphodiesterase (GpdQ) with chemically diverse substrates, i.e. phosphomono-, phosphodi-, and phosphotriester have been investigated using molecular dynamics (MD) simulations.

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

“…We studied the interactions of the reactive binuclear form of GpdQ with four chemically distinct substrates (NPP, BNPP, GPE, and paraoxon) using all‐atom MD simulations . The parameterization of these substrates was conducted using antechamber, an inbuilt tool in Amber .…”

“…15,[31][32][33][34][35][36] There are numerous examples of mono-and binuclear metal center containing metallohydrolases; however, the focus of this review is activities of two promiscuous enzymes; i.e., insulin degrading enzyme (IDE) and glycerophosphodiesterase (GpdQ). [37][38][39][40] IDE is a metallopeptidase that contains a Zn─N 2 O [Zn(His, His, Glu)] catalytic center, where N is the nitrogen atom from His and O is the oxygen atom from Glu (Figure 1). On the other hand, GpdQ is a phosphatase that possesses a binuclear Fe(N 2 O 2 )─M(N 2 O 2 ) [Fe(His, His, Asp, Asp)─M(His, His, Asp, Asn)] catalytic center, where N is the nitrogen atom from His and O is the oxygen atom from either Asp or Asn (Figure 1).…”

“…We studied the interactions of the reactive binuclear form of GpdQ with four chemically distinct substrates (NPP, BNPP, GPE, and paraoxon) using all-atom MD simulations. 40 The parameterization of these substrates was conducted using antechamber, 109 an inbuilt tool in Amber. 110 The docking procedures were executed using the AutoDock Vina 1.5.6 software utilizing both rigid and flexible docking protocols.…”

“…There are numerous examples of mono‐ and binuclear metal center containing metallohydrolases; however, the focus of this review is activities of two promiscuous enzymes; i.e., insulin degrading enzyme (IDE) and glycerophosphodiesterase (GpdQ) . IDE is a metallopeptidase that contains a Zn─N 2 O [Zn(His, His, Glu)] catalytic center, where N is the nitrogen atom from His and O is the oxygen atom from Glu (Figure ).…”

Rapid Biodegradation of the Organophosphorus Insecticide Chlorpyrifos by Cupriavidus nantongensis X1T

“…Meanwhile, the degradation ability of the strain is mainly the function of the degradation enzymes in vivo, and the change of temperature will significantly affect the activity of the degradation enzymes [39]. Compared with the optimum temperatures of other organophosphorus hydrolases MPH, PTE and GPD, strain X1 T has a higher utilization value in actual chlorpyrifos-contaminated soil remediation [40,41,42].…”