TY - CHAP
T1 - Biomarkers of exposure to organophosphorus poisons
T2 - A new motif for covalent binding to tyrosine in proteins that have no active site serine
AU - Lockridge, Oksana
AU - Schopfer, Lawrence M.
AU - Masson, Patrick
N1 - Funding Information:
Mass spectra were obtained with the support of the Mass Spectrometry and Proteomics core facility at the University of Nebraska Medical Center. This work was supported by US Army Medical Research and Material Command W81XWH-07-2-0034 (to OL), NIH CounterACT U01 NS058056-02 (to OL), NIH Eppley Cancer Center grant P30CA36727, and DGA grant 03co010-05/PEA01 08 7 (to P.M.).
PY - 2009
Y1 - 2009
N2 - A new motif for Organophosphorus (OP) binding to tyrosine has been identified. Almost all proteins appear to be capable of binding OP covalently on tyrosine. Whether or not OP will bind to tyrosine in vivo will depend on the concentration of the protein, the concentration of the OP, and the ionization status of the tyrosine hydroxyl group. The latter factor appears to be dependent on the presence of nearby positively charged residues. The importance of the first and third factors is amply demonstrated in the case of albumin. The concentration of albumin is so high that albumin binds OP even though its rate of reaction is slow. The reaction of albumin's most sensitive tyrosine is aided by the presence of three positively charged residues within a five-residue stretch surrounding that tyrosine. Identification of new biomarkers of OP exposure may also lead to an understanding of why some people are intoxicated by low doses of OP that have no effect on the majority of the population. The new motif for OP binding to tyrosine may lead to new antidotes for OP poisoning; for example, peptides containing several tyrosines and several arginines may be effective OP scavengers.
AB - A new motif for Organophosphorus (OP) binding to tyrosine has been identified. Almost all proteins appear to be capable of binding OP covalently on tyrosine. Whether or not OP will bind to tyrosine in vivo will depend on the concentration of the protein, the concentration of the OP, and the ionization status of the tyrosine hydroxyl group. The latter factor appears to be dependent on the presence of nearby positively charged residues. The importance of the first and third factors is amply demonstrated in the case of albumin. The concentration of albumin is so high that albumin binds OP even though its rate of reaction is slow. The reaction of albumin's most sensitive tyrosine is aided by the presence of three positively charged residues within a five-residue stretch surrounding that tyrosine. Identification of new biomarkers of OP exposure may also lead to an understanding of why some people are intoxicated by low doses of OP that have no effect on the majority of the population. The new motif for OP binding to tyrosine may lead to new antidotes for OP poisoning; for example, peptides containing several tyrosines and several arginines may be effective OP scavengers.
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U2 - 10.1016/B978-012374484-5.00056-0
DO - 10.1016/B978-012374484-5.00056-0
M3 - Chapter
AN - SCOPUS:84884763660
SN - 9780123744845
SP - 847
EP - 858
BT - Handbook of Toxicology of Chemical Warfare Agents
PB - Elsevier Inc.
ER -