4ngn
From Proteopedia
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<StructureSection load='4ngn' size='340' side='right'caption='[[4ngn]], [[Resolution|resolution]] 1.64Å' scene=''> | <StructureSection load='4ngn' size='340' side='right'caption='[[4ngn]], [[Resolution|resolution]] 1.64Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4ngn]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[4ngn]] 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=4NGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NGN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=J96:N-{[(1S)-1-carboxy-5-({[2-({4,44-dioxo-48-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-7,10,13,16,19,22,25,28,31,34,37,40-dodecaoxa-3,43-diazaoctatetracont-1-yl}oxy)phenyl]acetyl}amino)pentyl]carbamoyl}-L-glutamic+acid'>J96</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=J96:N-{[(1S)-1-carboxy-5-({[2-({4,44-dioxo-48-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-7,10,13,16,19,22,25,28,31,34,37,40-dodecaoxa-3,43-diazaoctatetracont-1-yl}oxy)phenyl]acetyl}amino)pentyl]carbamoyl}-L-glutamic+acid'>J96</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=4ngn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ngn OCA], [https://pdbe.org/4ngn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ngn RCSB], [https://www.ebi.ac.uk/pdbsum/4ngn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ngn ProSAT]</span></td></tr> | |
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| - | <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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), is an established prostate cancer marker and is considered a promising target for specific anticancer drug delivery. Low-molecular-weight inhibitors of GCPII are advantageous specific ligands for this purpose. However, they must be modified with a linker to enable connection of the ligand with an imaging molecule, anticancer drug, and/or nanocarrier. Here, we describe a structure-activity relationship (SAR) study of GCPII inhibitors with linkers suitable for imaging and drug delivery. Structure-assisted inhibitor design and targeting of a specific GCPII exosite resulted in a 7-fold improvement in Ki value compared to the parent structure. X-ray structural analysis of the inhibitor series led to the identification of several inhibitor binding modes. We also optimized the length of the inhibitor linker for effective attachment to a biotin-binding molecule and showed that the optimized inhibitor could be used to target nanoparticles to cells expressing GCPII. | ||
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| + | Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery.,Tykvart J, Schimer J, Barinkova J, Pachl P, Postova-Slavetinska L, Majer P, Konvalinka J, Sacha P Bioorg Med Chem. 2014 Aug 1;22(15):4099-108. doi: 10.1016/j.bmc.2014.05.061. Epub, 2014 Jun 5. PMID:24954515<ref>PMID:24954515</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4ngn" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Carboxypeptidase|Carboxypeptidase]] | + | *[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
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[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Pachl | + | [[Category: Pachl P]] |
| - | [[Category: Tykvart | + | [[Category: Tykvart J]] |
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Current revision
Crystal Structure of Glutamate Carboxypeptidase II in a complex with urea-based inhibitor
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