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''' | ==X-ray structure of of human glutamate carboxypeptidase II (GCPII) in a complex with COIBzL, a urea-based inhibitor (2S)-2-[({(1S)-1-carboxy-2-[(2S)-oxiran-2-yl]ethyl}carbamoyl)amino]-6-[(4-iodobenzoyl)amino]hexanoic acid== | ||
<StructureSection load='4oc1' size='340' side='right' caption='[[4oc1]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4oc1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OC1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OC1 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QS:(2S)-2-[({(1S)-1-CARBOXY-2-[(2S)-OXIRAN-2-YL]ETHYL}CARBAMOYL)AMINO]-6-[(4-IODOBENZOYL)AMINO]HEXANOIC+ACID+(NON-PREFERRED+NAME)'>2QS</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4oc0|4oc0]], [[4oc2|4oc2]], [[4oc3|4oc3]], [[4oc4|4oc4]], [[4oc5|4oc5]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamate_carboxypeptidase_II Glutamate carboxypeptidase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.21 3.4.17.21] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4oc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oc1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oc1 RCSB], [http://www.ebi.ac.uk/pdbsum/4oc1 PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Urea-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<ref>PMID:24731280</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Glutamate carboxypeptidase II]] | |||
[[Category: Barinka, C.]] | |||
[[Category: Byun, Y.]] | |||
[[Category: Cerny, J.]] | |||
[[Category: Lubkowski, J.]] | |||
[[Category: Pavlicek, J.]] | |||
[[Category: Pomper, M.]] | |||
[[Category: Ptacek, J.]] | |||
[[Category: Skultetyova, L.]] | |||
[[Category: Hydrolase]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Metallopeptidase]] | |||
Revision as of 11:59, 21 May 2014
X-ray structure of of human glutamate carboxypeptidase II (GCPII) in a complex with COIBzL, a urea-based inhibitor (2S)-2-[({(1S)-1-carboxy-2-[(2S)-oxiran-2-yl]ethyl}carbamoyl)amino]-6-[(4-iodobenzoyl)amino]hexanoic acidX-ray structure of of human glutamate carboxypeptidase II (GCPII) in a complex with COIBzL, a urea-based inhibitor (2S)-2-[({(1S)-1-carboxy-2-[(2S)-oxiran-2-yl]ethyl}carbamoyl)amino]-6-[(4-iodobenzoyl)amino]hexanoic acid
Structural highlights
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. References
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