Glutamate carboxypeptidase II

Glutamate carboxypeptidase II (GCP II) is a homodimeric dinuclear zinc carboxypeptidase catalysing the hydrolysis of substrates bearing L-glutamate at the C-terminal position. The GCP II-catalysed hydrolysis of the neuropeptide N-acetyl-L-aspartyl-L-glutamate is considered an important source of glutamate, whose excesses are associated with various neurological disorders. Additionally, an increased expression of GCP II is often detected in cancer. In this context, GCP II is currently a pharmacological and diagnostic target being pursued in the clinic for the regulation of glutamate and for imaging purposes. An overview on GCP II, including its reaction mechanism, its biological localisation and its physiological roles, is provided herein. The main classes of GCP II inhibitors, as well as recent advances in the development of potential therapeutic and diagnostic tools based on the inhibition and/or detection of GCP II are also described in this chapter.