2or4
From Proteopedia
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| - | [[Image:2or4.jpg|left|200px]] | + | [[Image:2or4.jpg|left|200px]] |
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| - | '''A high resolution crystal structure of human glutamate carboxypeptidase II in complex with quisqualic acid''' | + | {{Structure |
| + | |PDB= 2or4 |SIZE=350|CAPTION= <scene name='initialview01'>2or4</scene>, resolution 1.62Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <scene name='pdbligand=QUS:(S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC ACID'>QUS</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= FOLH1, FOLH, NAALAD1, PSM, PSMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''A high resolution crystal structure of human glutamate carboxypeptidase II in complex with quisqualic acid''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2OR4 is a [ | + | 2OR4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OR4 OCA]. |
==Reference== | ==Reference== | ||
| - | Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II., Barinka C, Rovenska M, Mlcochova P, Hlouchova K, Plechanovova A, Majer P, Tsukamoto T, Slusher BS, Konvalinka J, Lubkowski J, J Med Chem. 2007 Jul 12;50(14):3267-73. Epub 2007 Jun 14. PMID:[http:// | + | Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II., Barinka C, Rovenska M, Mlcochova P, Hlouchova K, Plechanovova A, Majer P, Tsukamoto T, Slusher BS, Konvalinka J, Lubkowski J, J Med Chem. 2007 Jul 12;50(14):3267-73. Epub 2007 Jun 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17567119 17567119] |
[[Category: Glutamate carboxypeptidase II]] | [[Category: Glutamate carboxypeptidase II]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: prostate specific membrane antigen]] | [[Category: prostate specific membrane antigen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:03:30 2008'' |
Revision as of 16:03, 20 March 2008
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| , resolution 1.62Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , and | ||||||
| Gene: | FOLH1, FOLH, NAALAD1, PSM, PSMA (Homo sapiens) | ||||||
| Activity: | Glutamate carboxypeptidase II, with EC number 3.4.17.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
A high resolution crystal structure of human glutamate carboxypeptidase II in complex with quisqualic acid
Contents |
Overview
Inhibition of glutamate carboxypeptidase II (GCPII) has been shown to be neuroprotective in multiple preclinical models in which dysregulated glutamatergic transmission is implicated. Herein, we report crystal structures of the human GCPII complexed with three glutamate mimetics/derivatives, 2-(phosphonomethyl)pentanedioic acid (2-PMPA), quisqualic acid (QA), and L-serine O-sulfate (L-SOS), at 1.72, 1.62, and 2.10 A resolution, respectively. Despite the structural differences between the distal parts of the inhibitors, all three compounds share similar binding modes in the pharmacophore (i.e., S1') pocket of GCPII, where they are stabilized by a combination of polar and van der Waals interactions. The structural diversity of the distal parts of the inhibitors leads to rearrangements of the S1' site that are necessary for efficient interactions between the enzyme and an inhibitor. The set of structures presented here, in conjunction with the available biochemical data, illustrates a flexibility of the GCPII pharmacophore pocket and highlights the structural features required for potent GCPII inhibition. These findings could facilitate the rational structure-based drug design of new GCPII inhibitors in the future.
Disease
Known diseases associated with this structure: Myocardial infarcation, susceptibility to OMIM:[602855]
About this Structure
2OR4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II., Barinka C, Rovenska M, Mlcochova P, Hlouchova K, Plechanovova A, Majer P, Tsukamoto T, Slusher BS, Konvalinka J, Lubkowski J, J Med Chem. 2007 Jul 12;50(14):3267-73. Epub 2007 Jun 14. PMID:17567119
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