Structural highlights
4x3r is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , , , |
| Activity: | Glutamate carboxypeptidase II, with EC number 3.4.17.21 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Function
[FOLH1_HUMAN] Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate. Isoform PSM-4 and isoform PSM-5 would appear to be physiologically irrelevant. Involved in prostate tumor progression. Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.
Publication Abstract from PubMed
We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active toward GCPII than its closest human homologue, glutamate carboxypeptidase III (GCPIII). Additionally, we demonstrate that the prepared inhibitor conjugate can be used for sensitive and selective imaging of GCPII in mammalian cells.
Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II.,Tykvart J, Schimer J, Jancarik A, Barinkova J, Navratil V, Starkova J, Sramkova K, Konvalinka J, Majer P, Sacha P J Med Chem. 2015 May 28;58(10):4357-63. doi: 10.1021/acs.jmedchem.5b00278. Epub, 2015 May 7. PMID:25923815[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tykvart J, Schimer J, Jancarik A, Barinkova J, Navratil V, Starkova J, Sramkova K, Konvalinka J, Majer P, Sacha P. Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II. J Med Chem. 2015 May 28;58(10):4357-63. doi: 10.1021/acs.jmedchem.5b00278. Epub, 2015 May 7. PMID:25923815 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00278
