| Structural highlights
3nh5 is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 3nfz, 3nh4, 3nh8 |
| Gene: | ACY-3, Acy3, Aspa2 (Mus musculus) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[ACY3_MOUSE] Plays an important role in deacetylating mercapturic acids in kidney proximal tubules. Also acts on N-acetyl-aromatic amino acids.[1] [2]
Publication Abstract from PubMed
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.
Structures of aminoacylase 3 in complex with acetylated substrates.,Hsieh JM, Tsirulnikov K, Sawaya MR, Magilnick N, Abuladze N, Kurtz I, Abramson J, Pushkin A Proc Natl Acad Sci U S A. 2010 Oct 4. PMID:20921362[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pushkin A, Carpenito G, Abuladze N, Newman D, Tsuprun V, Ryazantsev S, Motemoturu S, Sassani P, Solovieva N, Dukkipati R, Kurtz I. Structural characterization, tissue distribution, and functional expression of murine aminoacylase III. Am J Physiol Cell Physiol. 2004 Apr;286(4):C848-56. Epub 2003 Dec 3. PMID:14656720 doi:http://dx.doi.org/10.1152/ajpcell.00192.2003
- ↑ Newman D, Abuladze N, Scholz K, Dekant W, Tsuprun V, Ryazantsev S, Bondar G, Sassani P, Kurtz I, Pushkin A. Specificity of aminoacylase III-mediated deacetylation of mercapturic acids. Drug Metab Dispos. 2007 Jan;35(1):43-50. Epub 2006 Sep 29. PMID:17012540 doi:http://dx.doi.org/10.1124/dmd.106.012062
- ↑ Hsieh JM, Tsirulnikov K, Sawaya MR, Magilnick N, Abuladze N, Kurtz I, Abramson J, Pushkin A. Structures of aminoacylase 3 in complex with acetylated substrates. Proc Natl Acad Sci U S A. 2010 Oct 4. PMID:20921362 doi:10.1073/pnas.1006687107
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