van der Schans M

References (2)

Title : Structural study of the complex stereoselectivity of human butyrylcholinesterase for the neurotoxic V-agents - Wandhammer_2011_J.Biol.Chem_286_16783
Author(s) : Wandhammer M , Carletti E , van der Schans M , Gillon E , Nicolet Y , Masson P , Goeldner M , Noort D , Nachon F
Ref : Journal of Biological Chemistry , 286 :16783 , 2011
Abstract : Nerve agents are chiral organophosphate compounds (OPs) that exert their acute toxicity by phosphorylating the catalytic serine of acetylcholinesterase (AChE). The inhibited cholinesterases can be reactivated using oximes, but a spontaneous time-dependent process called aging alters the adduct, leading to resistance toward oxime reactivation. Human butyrylcholinesterase (BChE) functions as a bioscavenger, protecting the cholinergic system against OPs. The stereoselectivity of BChE is an important parameter for its efficiency at scavenging the most toxic OPs enantiomer for AChE. Crystals of BChE inhibited in solution or in cristallo with racemic V-agents (VX, Russian VX, and Chinese VX) systematically show the formation of the P(S) adduct. In this configuration, no catalysis of aging seems possible as confirmed by the three-dimensional structures of the three conjugates incubated over a period exceeding a week. Crystals of BChE soaked in optically pure VX(R)-(+) and VX(S)-(-) solutions lead to the formation of the P(S) and P(R) adduct, respectively. These structural data support an in-line phosphonylation mechanism. Additionally, they show that BChE reacts with VX(R)-(+) in the presence of racemic mixture of V-agents, at odds with earlier kinetic results showing a moderate higher inhibition rate for VX(S)-(-). These combined results suggest that the simultaneous presence of both enantiomers alters the enzyme stereoselectivity. In summary, the three-dimensional data show that BChE reacts preferentially with P(R) enantiomer of V-agents and does not age, in complete contrast to AChE, which is selectively inhibited by the P(S) enantiomer and ages.
ESTHER : Wandhammer_2011_J.Biol.Chem_286_16783
PubMedSearch : Wandhammer_2011_J.Biol.Chem_286_16783
PubMedID: 21454498
Gene_locus related to this paper: human-BCHE

Title : Development of an automated on-line pepsin digestion-liquid chromatography-tandem mass spectrometry configuration for the rapid analysis of protein adducts of chemical warfare agents - Carol-Visser_2008_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_870_91
Author(s) : Carol-Visser J , van der Schans M , Fidder A , Hulst AG , van Baar BL , Irth H , Noort D
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 870 :91 , 2008
Abstract : Rapid monitoring and retrospective verification are key issues in protection against and non-proliferation of chemical warfare agents (CWA). Such monitoring and verification are adequately accomplished by the analysis of persistent protein adducts of these agents. Liquid chromatography-mass spectrometry (LC-MS) is the tool of choice in the analysis of such protein adducts, but the overall experimental procedure is quite elaborate. Therefore, an automated on-line pepsin digestion-LC-MS configuration has been developed for the rapid determination of CWA protein adducts. The utility of this configuration is demonstrated by the analysis of specific adducts of sarin and sulfur mustard to human butyryl cholinesterase and human serum albumin, respectively.
ESTHER : Carol-Visser_2008_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_870_91
PubMedSearch : Carol-Visser_2008_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_870_91
PubMedID: 18573700