3NFZ

Crystal structure of murine aminoacylase 3 in complex with N-acetyl-L-tyrosine

Summary for 3NFZ

• Entry DOI: 10.2210/pdb3nfz/pdb
• Related: 3NH4 3NH5 3NH8
• Descriptor: Aspartoacylase-2, ZINC ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: n-acetyl-l-tryosine, hydrolase
• Biological source: Mus musculus (mouse)
• Cellular location: Apical cell membrane; Peripheral membrane protein: Q91XE4
• Total number of polymer chains: 1
• Total formula weight: 36794.92

Authors

Hsieh, J.M.,Tsirulnikov, K.,Sawaya, M.R.,Magilnick, N.,Abuladze, N.,Kurtz, I.,Abramson, J.,Pushkin, A. (deposition date: 2010-06-10, release date: 2010-10-20, Last modification date: 2024-04-03)

Primary citation

Hsieh, J.M.,Tsirulnikov, K.,Sawaya, M.R.,Magilnick, N.,Abuladze, N.,Kurtz, I.,Abramson, J.,Pushkin, A.
Structures of aminoacylase 3 in complex with acetylated substrates.
Proc.Natl.Acad.Sci.USA, 107:17962-17967, 2010

PubMed 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.

PubMed: 20921362
DOI: 10.1073/pnas.1006687107

Experimental method

X-RAY DIFFRACTION (2.147 Å)