2c6g: Difference between revisions

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-{{Seed}}
-[[Image:2c6g.png|left|200px]]
-<!--
+==Membrane-bound glutamate carboxypeptidase II (GCPII) with bound glutamate==
-The line below this paragraph, containing "STRUCTURE_2c6g", creates the "Structure Box" on the page.
+<StructureSection load='2c6g' size='340' side='right'caption='[[2c6g]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2c6g]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C6G FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_2c6g|  PDB=2c6g  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c6g OCA], [https://pdbe.org/2c6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c6g RCSB], [https://www.ebi.ac.uk/pdbsum/2c6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c6g ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/FOLH1_HUMAN FOLH1_HUMAN] Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate. Isoform PSM-4 and isoform PSM-5 would appear to be physiologically irrelevant. Involved in prostate tumor progression.  Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/2c6g_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2c6g ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-===MEMBRANE-BOUND GLUTAMATE CARBOXYPEPTIDASE II (GCPII) WITH BOUND GLUTAMATE===
+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<ref>PMID:16467855</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2c6g" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_16467855}}, adds the Publication Abstract to the page
+*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 16467855 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_16467855}}
+__TOC__
+</StructureSection>
-==About this Structure==
-C6G is a 1 chain 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=2C6G OCA].
-==Reference==
-<ref group="xtra">PMID:16467855</ref><references group="xtra"/>
-[[Category: Glutamate carboxypeptidase II]]
 [[Category: Homo sapiens]]
-[[Category: Barinka, C.]]
+[[Category: Large Structures]]
-[[Category: Hilgenfeld, R.]]
+[[Category: Barinka C]]
-[[Category: Konvalinka, J.]]
+[[Category: Hilgenfeld R]]
-[[Category: Li, W.]]
+[[Category: Konvalinka J]]
-[[Category: Majer, P.]]
+[[Category: Li W]]
-[[Category: Mesters, J R.]]
+[[Category: Majer P]]
-[[Category: Slusher, B S.]]
+[[Category: Mesters JR]]
-[[Category: Tsukamoto, T.]]
+[[Category: Slusher BS]]
-[[Category: Alternative splicing]]
+[[Category: Tsukamoto T]]
-[[Category: Antigen]]
-[[Category: Carboxypeptidase]]
-[[Category: Dipeptidase]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Metal-binding]]
-[[Category: Metalloprotease]]
-[[Category: Multifunctional enzyme]]
-[[Category: Naaladase]]
-[[Category: Neurodegenerative disease]]
-[[Category: Peptidase]]
-[[Category: Polymorphism]]
-[[Category: Prostate cancer]]
-[[Category: Psma]]
-[[Category: Signal-anchor]]
-[[Category: Transmembrane]]
-[[Category: Zinc]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 12:13:33 2009''