| First Author | Hsieh JM | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 42 | Pages | 17962-7 |
| PubMed ID | 20921362 | Mgi Jnum | J:165543 |
| Mgi Id | MGI:4837619 | Doi | 10.1073/pnas.1006687107 |
| Citation | Hsieh JM, et al. (2010) Structures of aminoacylase 3 in complex with acetylated substrates. Proc Natl Acad Sci U S A 107(42):17962-7 |
| abstractText | 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(alpha)-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. |
