Structural highlights
3iww is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , , , |
| Gene: | FOLH1, FOLH, NAALAD1, PSM, PSMA (HUMAN) |
| Activity: | Glutamate carboxypeptidase II, with EC number 3.4.17.21 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We report a strategy based on bioisosterism to improve the physicochemical properties of existing hydrophilic, urea-based GCPII inhibitors. Comprehensive structure-activity relationship studies of the P1' site of ZJ-43- and DCIBzL-based compounds identified several glutamate-free inhibitors with K(i) values below 20nM. Among them, compound 32d (K(i)=11nM) exhibited selective uptake in GCPII-expressing tumors by SPECT-CT imaging in mice. A novel conformational change of amino acids in the S1' pharmacophore pocket was observed in the X-ray crystal structure of GCPII complexed with 32d.
Bioisosterism of urea-based GCPII inhibitors: Synthesis and structure-activity relationship studies.,Wang H, Byun Y, Barinka C, Pullambhatla M, Bhang HE, Fox JJ, Lubkowski J, Mease RC, Pomper MG Bioorg Med Chem Lett. 2010 Jan 1;20(1):392-7. Epub 2009 Oct 24. PMID:19897367[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang H, Byun Y, Barinka C, Pullambhatla M, Bhang HE, Fox JJ, Lubkowski J, Mease RC, Pomper MG. Bioisosterism of urea-based GCPII inhibitors: Synthesis and structure-activity relationship studies. Bioorg Med Chem Lett. 2010 Jan 1;20(1):392-7. Epub 2009 Oct 24. PMID:19897367 doi:10.1016/j.bmcl.2009.10.061
