In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 107, No. 42 ( 2010-10-19), p. 17962-17967
Abstract:
Trichloroethylene (TCE) is one of the most widespread environmental contaminants, which is metabolized to N -acetyl- S -1,2-dichlorovinyl- l -cysteine (NA-DCVC) before being excreted in the urine. Alternatively, NA-DCVC can be deacetylated by aminoacylase 3 (AA3), an enzyme that is highly expressed in the kidney, liver, and brain. NA-DCVC deacetylation initiates the transformation into toxic products that ultimately causes acute renal failure. AA3 inhibition is therefore a target of interest to prevent TCE induced nephrotoxicity. Here we report the crystal structure of recombinant mouse AA3 (mAA3) in the presence of its acetate byproduct and two substrates: N α -acetyl- l -tyrosine and NA-DCVC. These structures, in conjunction with biochemical data, indicated that AA3 mediates substrate specificity through van der Waals interactions providing a dynamic interaction interface, which facilitates a diverse range of substrates.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1006687107
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2010
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
