Many human enzymes serve as targets for the action of pharmaceutically active compounds. Several classes of human enzymes that serve as such targets include helicase, steroid esterase and sulfatase, convertase, synthase, dehydrogenase, monoxygenase, transferase, kinase, glutanase, decarboxylase, isomerase and reductase. It is therefore important in developing new pharmaceutical compounds to identify target enzyme proteins that can be put into high-throughput screening formats. The present invention advances the state of the art by providing novel human drug target enzymes related to the aminoacylase subfamily.
The present invention has a substantial similarity to aminoacylase-1. Aminoacylase-1 (ACY1, EC 3.5.1.14), a new type of metalloprotein, is a cytosolic enzyme with a wide range of tissue expression and has been postulated to function in the catabolism and salvage of acylated amino acids. ACY-1 is more highly expressed in kidney than in liver. ACY1 has been assigned to chromosome 3p21, a region reduced to homozygosity in small-cell lung cancer and renal cell carcinoma, and shows a reduced or absent expression in small-cell lung cancer cell lines and tumors. For a review related to aminoacylase-1, see Miller et al., Genomics 1990 Sep.; 8(1):149-54, Mitta et al., J Biochem (Tokyo) 1992 Dec.; 112(6):737-42.
Enzyme proteins, particularly members of the aminoacylase subfamily, are a major target for drug action and development. Accordingly, it is valuable to the field of pharmaceutical development to identify and characterize previously unknown members of this subfamily of enzyme proteins. The present invention advances the state of the art by providing previously unidentified human enzyme proteins, and the polynucleotides encoding them, that have homology to members of the aminoacylase subfamily. These novel compositions are useful in the diagnosis, prevention and treatment of biological processes associated with human diseases.