4oc2: Difference between revisions
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<StructureSection load='4oc2' size='340' side='right'caption='[[4oc2]], [[Resolution|resolution]] 1.65Å' scene=''> | <StructureSection load='4oc2' size='340' side='right'caption='[[4oc2]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4oc2]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4oc2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OC2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OC2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QQ:N~2~-{[(1S)-1-CARBOXYBUT-3-YN-1-YL]CARBAMOYL}-N~6~-(4-IODOBENZOYL)-L-LYSINE'>2QQ</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2QQ:N~2~-{[(1S)-1-CARBOXYBUT-3-YN-1-YL]CARBAMOYL}-N~6~-(4-IODOBENZOYL)-L-LYSINE'>2QQ</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4oc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oc2 OCA], [https://pdbe.org/4oc2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oc2 RCSB], [https://www.ebi.ac.uk/pdbsum/4oc2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oc2 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/FOLH1_HUMAN 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. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Carboxypeptidase|Carboxypeptidase]] | *[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Barinka | [[Category: Barinka C]] | ||
[[Category: Byun | [[Category: Byun Y]] | ||
[[Category: Cerny | [[Category: Cerny J]] | ||
[[Category: Lubkowski | [[Category: Lubkowski J]] | ||
[[Category: Pavlicek | [[Category: Pavlicek J]] | ||
[[Category: Pomper | [[Category: Pomper M]] | ||
[[Category: Ptacek | [[Category: Ptacek J]] | ||
[[Category: Skultetyova | [[Category: Skultetyova L]] | ||
Latest revision as of 13:22, 30 October 2024
X-ray structure of of human glutamate carboxypeptidase II (GCPII) in a complex with CEIBzL, a urea-based inhibitor N~2~-{[(1S)-1-carboxybut-3-yn-1-yl]carbamoyl}-N~6~-(4-iodobenzoyl)-L-lysineX-ray structure of of human glutamate carboxypeptidase II (GCPII) in a complex with CEIBzL, a urea-based inhibitor N~2~-{[(1S)-1-carboxybut-3-yn-1-yl]carbamoyl}-N~6~-(4-iodobenzoyl)-L-lysine
Structural highlights
FunctionFOLH1_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 PubMedUrea-based inhibitors of human glutamate carboxypeptidase II (GCPII) have advanced into clinical trials for imaging metastatic prostate cancer. In parallel efforts, agents with increased lipophilicity have been designed and evaluated for targeting GCPII residing within the neuraxis. Here we report the structural and computational characterization of six complexes between GCPII and P1'-diversified urea-based inhibitors that have the C-terminal glutamate replaced by more hydrophobic moieties. The X-ray structures are complemented by quantum mechanics calculations that provide a quantitative insight into the GCPII/inhibitor interactions. These data can be used for the rational design of novel glutamate-free GCPII inhibitors with tailored physicochemical properties. Structural characterization of P1'-diversified urea-based inhibitors of glutamate carboxypeptidase II.,Pavlicek J, Ptacek J, Cerny J, Byun Y, Skultetyova L, Pomper MG, Lubkowski J, Barinka C Bioorg Med Chem Lett. 2014 May 15;24(10):2340-5. doi: 10.1016/j.bmcl.2014.03.066., Epub 2014 Mar 28. PMID:24731280[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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