Title : Human
glutamate carboxypeptidase II inhibition: structures of
GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA
Abstract :
- Human glutamate carboxypeptidase II ( GCPII ) occurs in the central nervous system as well as in human prostate (where it is called prostate-specific membrane antigen ; PSMA )
- Inhibitors of the enzyme have been shown to provide neuroprotection, but may also be useful for the detection, imaging and treatment of prostate cancer
- Crystal structures were determined of the extracellular part of GCPII (amino-acid residues 44-750 ) in complex with two potent inhibitors, quisqualate and 2-PMPA (the strongest GCPII inhibitor to date), at resolutions of 3.0 and 2.2 A, respectively
- In addition, models were constructed for binding of the inhibitors willardiine, homoibotenate, L-2-amino-4-phosphonobutanoic acid and L- serine-O-sulfate to the S1' site of the enzyme
- The common denominator for high-affinity binding to the S1' site is the formation of two strong salt bridges
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protein,
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Output(Part-Of) (sent_index,
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*Output_Site_Fusion* (sent_index,
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