2or4
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2or4.jpg|left|200px]] | [[Image:2or4.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2or4", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_2or4| PDB=2or4 | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''A high resolution crystal structure of human glutamate carboxypeptidase II in complex with quisqualic acid''' | '''A high resolution crystal structure of human glutamate carboxypeptidase II in complex with quisqualic acid''' | ||
| Line 28: | Line 25: | ||
[[Category: Barinka, C.]] | [[Category: Barinka, C.]] | ||
[[Category: Lubkowski, J.]] | [[Category: Lubkowski, J.]] | ||
| - | [[Category: | + | [[Category: Folate hydrolase]] |
| - | [[Category: | + | [[Category: Glutamate carboxypeptidase ii]] |
| - | [[Category: | + | [[Category: Metallopeptidase]] |
| - | [[Category: | + | [[Category: Naaladase]] |
| - | [[Category: | + | [[Category: Prostate specific membrane antigen]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 11:30:05 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 08:30, 4 May 2008
A high resolution crystal structure of human glutamate carboxypeptidase II in complex with quisqualic acid
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.
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 Page seeded by OCA on Sun May 4 11:30:05 2008
