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Title: Structural and Biochemical Characterization of Organotin and Organolead Compounds Binding to the Organomercurial Lyase MerB Provide New Insights into Its Mechanism of Carbon–Metal Bond Cleavage

Abstract

The organomercurial lyase MerB has the unique ability to cleave carbon–Hg bonds, and structural studies indicate that three residues in the active site (C96, D99, and C159 in E. coli MerB) play important roles in the carbon–Hg bond cleavage. However, the role of each residue in carbon–metal bond cleavage has not been well-defined. To do so, we have structurally and biophysically characterized the interaction of MerB with a series of organotin and organolead compounds. Studies with two known inhibitors of MerB, dimethyltin (DMT) and triethyltin (TET), reveal that they inhibit by different mechanisms. In both cases the initial binding is to D99, but DMT subsequently binds to C96, which induces a conformation change in the active site. In contrast, diethyltin (DET) is a substrate for MerB and the SnIV product remains bound in the active site in a coordination similar to that of HgII following cleavage of organomercurial compounds. The results with analogous organolead compounds are similar in that trimethyllead (TML) is not cleaved and binds only to D99, whereas diethyllead (DEL) is a substrate and the PbIV product remains bound in the active site. Binding and cleavage is an exothermic reaction, while binding to D99 has negligible net heatmore » flow. These results show that initial binding of organometallic compounds to MerB occurs at D99 followed, in some cases, by cleavage and loss of the organic moieties and binding of the metal ion product to C96, D99, and C159. The N-terminus of MerA is able to extract the bound PbVI but not the bound SnIV. These results suggest that MerB could be utilized for bioremediation applications, but certain organolead and organotin compounds may present an obstacle by inhibiting the enzyme.« less

Authors:
 [1];  [2];  [3];  [3]; ORCiD logo [2]; ORCiD logo [3]
  1. Département de Biochimie et Médicine Moléculaire, Université de Montréal, Montréal, Quebec H3C 3J7 Canada; Faculty of Pharmacy, Beni-suef University, Beni-suef, Egypt
  2. Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, United States
  3. Département de Biochimie et Médicine Moléculaire, Université de Montréal, Montréal, Quebec H3C 3J7 Canada
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1409605
Report Number(s):
BNL-114657-2017-JA¿¿¿
Journal ID: ISSN 0002-7863
DOE Contract Number:  
SC0012704
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of the American Chemical Society; Journal Volume: 139; Journal Issue: 2
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Wahba, Haytham M., Stevenson, Michael J., Mansour, Ahmed, Sygusch, Jurgen, Wilcox, Dean E., and Omichinski, James G.. Structural and Biochemical Characterization of Organotin and Organolead Compounds Binding to the Organomercurial Lyase MerB Provide New Insights into Its Mechanism of Carbon–Metal Bond Cleavage. United States: N. p., 2017. Web. doi:10.1021/jacs.6b11327.
Wahba, Haytham M., Stevenson, Michael J., Mansour, Ahmed, Sygusch, Jurgen, Wilcox, Dean E., & Omichinski, James G.. Structural and Biochemical Characterization of Organotin and Organolead Compounds Binding to the Organomercurial Lyase MerB Provide New Insights into Its Mechanism of Carbon–Metal Bond Cleavage. United States. doi:10.1021/jacs.6b11327.
Wahba, Haytham M., Stevenson, Michael J., Mansour, Ahmed, Sygusch, Jurgen, Wilcox, Dean E., and Omichinski, James G.. Tue . "Structural and Biochemical Characterization of Organotin and Organolead Compounds Binding to the Organomercurial Lyase MerB Provide New Insights into Its Mechanism of Carbon–Metal Bond Cleavage". United States. doi:10.1021/jacs.6b11327.
@article{osti_1409605,
title = {Structural and Biochemical Characterization of Organotin and Organolead Compounds Binding to the Organomercurial Lyase MerB Provide New Insights into Its Mechanism of Carbon–Metal Bond Cleavage},
author = {Wahba, Haytham M. and Stevenson, Michael J. and Mansour, Ahmed and Sygusch, Jurgen and Wilcox, Dean E. and Omichinski, James G.},
abstractNote = {The organomercurial lyase MerB has the unique ability to cleave carbon–Hg bonds, and structural studies indicate that three residues in the active site (C96, D99, and C159 in E. coli MerB) play important roles in the carbon–Hg bond cleavage. However, the role of each residue in carbon–metal bond cleavage has not been well-defined. To do so, we have structurally and biophysically characterized the interaction of MerB with a series of organotin and organolead compounds. Studies with two known inhibitors of MerB, dimethyltin (DMT) and triethyltin (TET), reveal that they inhibit by different mechanisms. In both cases the initial binding is to D99, but DMT subsequently binds to C96, which induces a conformation change in the active site. In contrast, diethyltin (DET) is a substrate for MerB and the SnIV product remains bound in the active site in a coordination similar to that of HgII following cleavage of organomercurial compounds. The results with analogous organolead compounds are similar in that trimethyllead (TML) is not cleaved and binds only to D99, whereas diethyllead (DEL) is a substrate and the PbIV product remains bound in the active site. Binding and cleavage is an exothermic reaction, while binding to D99 has negligible net heat flow. These results show that initial binding of organometallic compounds to MerB occurs at D99 followed, in some cases, by cleavage and loss of the organic moieties and binding of the metal ion product to C96, D99, and C159. The N-terminus of MerA is able to extract the bound PbVI but not the bound SnIV. These results suggest that MerB could be utilized for bioremediation applications, but certain organolead and organotin compounds may present an obstacle by inhibiting the enzyme.},
doi = {10.1021/jacs.6b11327},
journal = {Journal of the American Chemical Society},
number = 2,
volume = 139,
place = {United States},
year = {Tue Jan 03 00:00:00 EST 2017},
month = {Tue Jan 03 00:00:00 EST 2017}
}