Biomedical Engineering Reference
In-Depth Information
CHAPTER 3
Glutamate Carboxypeptidase II
as a Therapeutic Target
KLA
´
RA HLOUCHOVA
´
,
a
CYRIL BAR
ˇ
INKA
b
AND
JAN KONVALINKA*
a
a
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of
the Czech Republic, Flemingovo n. 2, 166 10 Praha 6, Czech Republic;
b
Institute of Biotechnology, Academy of Sciences of the Czech Republic,
Videnska 1093, 140 00 Praha 4, Czech Republic
3.1 Introduction
Glutamate carboxypeptidase II (GCPII; EC 3.4.17.21), a Zn
21
-dependent
metalloprotease of the M28 peptidase family, is a type II transmembrane
glycoprotein. GCPII is also known as prostate-specific membrane antigen
(PSMA) or folate hydrolase I (FOLH1), and the human protein consists of
750 amino acids. GCPII was initially identified as the antigen recognized by
the monoclonal antibody 7E11-C5, which was raised against a preparation
from LNCaP cells, a cell-culture line derived from human-prostate adeno-
carcinoma,
1
hence its original designation PSMA. Independently, the rat
ortholog was identified as an exopeptidase responsible for cleavage of the
peptide neurotransmitter N-acetyl-
L
-aspartyl-
L
-glutamate (NAAG) into N-
acetyl-
L
-aspartate and free glutamate, the most potent neurotransmitter
in the CNS.
2
Because of this activity, the shortened name of NAALADase
