2c6c

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[[Image:2c6c.gif|left|200px]]<br /><applet load="2c6c" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2c6c.gif|left|200px]]
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caption="2c6c, resolution 2.00&Aring;" />
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'''MEMBRANE-BOUND GLUTAMATE CARBOXYPEPTIDASE II (GCPII) IN COMPLEX WITH GPI-18431 (S)-2-(4-IODOBENZYLPHOSPHONOMETHYL)-PENTANEDIOIC ACID'''<br />
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{{Structure
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|PDB= 2c6c |SIZE=350|CAPTION= <scene name='initialview01'>2c6c</scene>, resolution 2.00&Aring;
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|SITE= <scene name='pdbsite=AC1:24i+Binding+Site+For+Chain+A'>AC1</scene>
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|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=24I:(2S)-2-{[HYDROXY(4-IODOBENZYL)PHOSPHORYL]METHYL}PENTANEDIOIC ACID'>24I</scene>
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|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]
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|GENE=
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}}
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'''MEMBRANE-BOUND GLUTAMATE CARBOXYPEPTIDASE II (GCPII) IN COMPLEX WITH GPI-18431 (S)-2-(4-IODOBENZYLPHOSPHONOMETHYL)-PENTANEDIOIC ACID'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2C6C 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=24I:'>24I</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 Site: <scene name='pdbsite=AC1:24i+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C6C OCA].
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2C6C 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=2C6C OCA].
==Reference==
==Reference==
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Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer., Mesters JR, Barinka C, Li W, Tsukamoto T, Majer P, Slusher BS, Konvalinka J, Hilgenfeld R, EMBO J. 2006 Mar 22;25(6):1375-84. Epub 2006 Feb 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16467855 16467855]
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Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer., Mesters JR, Barinka C, Li W, Tsukamoto T, Majer P, Slusher BS, Konvalinka J, Hilgenfeld R, EMBO J. 2006 Mar 22;25(6):1375-84. Epub 2006 Feb 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16467855 16467855]
[[Category: Glutamate carboxypeptidase II]]
[[Category: Glutamate carboxypeptidase II]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: zinc]]
[[Category: zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:45:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:11:22 2008''

Revision as of 14:11, 20 March 2008

Image:2c6c.gif


PDB ID 2c6c

Drag the structure with the mouse to rotate
, resolution 2.00Å
Sites:
Ligands: , , , and
Activity: Glutamate carboxypeptidase II, with EC number 3.4.17.21
Coordinates: save as pdb, mmCIF, xml



MEMBRANE-BOUND GLUTAMATE CARBOXYPEPTIDASE II (GCPII) IN COMPLEX WITH GPI-18431 (S)-2-(4-IODOBENZYLPHOSPHONOMETHYL)-PENTANEDIOIC ACID


Contents

Overview

Membrane-bound glutamate carboxypeptidase II (GCPII) is a zinc metalloenzyme that catalyzes the hydrolysis of the neurotransmitter N-acetyl-L-aspartyl-L-glutamate (NAAG) to N-acetyl-L-aspartate and L-glutamate (which is itself a neurotransmitter). Potent and selective GCPII inhibitors have been shown to decrease brain glutamate and provide neuroprotection in preclinical models of stroke, amyotrophic lateral sclerosis, and neuropathic pain. Here, we report crystal structures of the extracellular part of GCPII in complex with both potent and weak inhibitors and with glutamate, the product of the enzyme's hydrolysis reaction, at 2.0, 2.4, and 2.2 A resolution, respectively. GCPII folds into three domains: protease-like, apical, and C-terminal. All three participate in substrate binding, with two of them directly involved in C-terminal glutamate recognition. One of the carbohydrate moieties of the enzyme is essential for homodimer formation of GCPII. The three-dimensional structures presented here reveal an induced-fit substrate-binding mode of this key enzyme and provide essential information for the design of GCPII inhibitors useful in the treatment of neuronal diseases and prostate cancer.

Disease

Known diseases associated with this structure: Myocardial infarcation, susceptibility to OMIM:[602855]

About this Structure

2C6C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer., Mesters JR, Barinka C, Li W, Tsukamoto T, Majer P, Slusher BS, Konvalinka J, Hilgenfeld R, EMBO J. 2006 Mar 22;25(6):1375-84. Epub 2006 Feb 9. PMID:16467855

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