2pvw
From Proteopedia
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==About this Structure== | ==About this Structure== | ||
| - | 2PVW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=G88:'>G88</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PVW OCA]. | + | 2PVW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=G88:'>G88</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Sites: <scene name='pdbsite=AC1:Nag+Binding+Site+For+Residue+A+1755'>AC1</scene>, <scene name='pdbsite=AC2:Nag+Binding+Site+For+Residue+A+1756'>AC2</scene>, <scene name='pdbsite=AC3:Nag+Binding+Site+For+Residue+A+1757'>AC3</scene>, <scene name='pdbsite=AC4:Nag+Binding+Site+For+Residue+A+1758'>AC4</scene>, <scene name='pdbsite=AC5:Nag+Binding+Site+For+Residue+A+1767'>AC5</scene>, <scene name='pdbsite=AC6:Nag+Binding+Site+For+Residue+A+1759'>AC6</scene>, <scene name='pdbsite=AC7:Nag+Binding+Site+For+Residue+A+1760'>AC7</scene>, <scene name='pdbsite=AC8:Nag+Binding+Site+For+Residue+A+1761'>AC8</scene>, <scene name='pdbsite=AC9:Nag+Binding+Site+For+Residue+A+1763'>AC9</scene>, <scene name='pdbsite=BC1:Nag+Binding+Site+For+Residue+A+1764'>BC1</scene>, <scene name='pdbsite=BC2:Bma+Binding+Site+For+Residue+A+1765'>BC2</scene>, <scene name='pdbsite=BC3:Man+Binding+Site+For+Residue+A+1766'>BC3</scene>, <scene name='pdbsite=BC4:Zn+Binding+Site+For+Residue+A+1751'>BC4</scene>, <scene name='pdbsite=BC5:Zn+Binding+Site+For+Residue+A+1752'>BC5</scene>, <scene name='pdbsite=BC6:Ca+Binding+Site+For+Residue+A+1753'>BC6</scene>, <scene name='pdbsite=BC7:Cl+Binding+Site+For+Residue+A+1754'>BC7</scene> and <scene name='pdbsite=BC8:G88+Binding+Site+For+Residue+A+1768'>BC8</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PVW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
| - | [[Category: | + | [[Category: 2-(phosphonomethyl)pentanedioic acid]] |
| + | [[Category: 2-(pmpa)]] | ||
| + | [[Category: folate hydrolase]] | ||
| + | [[Category: glutamate carboxypeptidase ii]] | ||
| + | [[Category: metallopeptidase]] | ||
| + | [[Category: naaladase]] | ||
| + | [[Category: prostate specific membrane antigen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 5 13:25:36 2008'' |
Revision as of 11:25, 5 March 2008
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A high resolution structure of human glutamate carboxypeptidase II (GCPII) in complex with 2-(phosphonomethyl)pentanedioic acid (2-PMPA)
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
2PVW is a Single protein structure of sequence from Homo sapiens with , , , and as ligands. Active as Glutamate carboxypeptidase II, with EC number 3.4.17.21 Known structural/functional Sites: , , , , , , , , , , , , , , , and . 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 Wed Mar 5 13:25:36 2008
