3fee: Difference between revisions

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-{{Seed}}
-[[Image:3fee.png|left|200px]]
-<!--
+==The high resolution structure of human glutamate carboxypeptidase III (GCPIII/NAALADase II) in complex with quisqualic acid==
-The line below this paragraph, containing "STRUCTURE_3fee", creates the "Structure Box" on the page.
+<StructureSection load='3fee' size='340' side='right'caption='[[3fee]], [[Resolution|resolution]] 1.56&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'>[[3fee]] 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=3FEE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FEE 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]] 1.56&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QUS:(S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC+ACID'>QUS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_3fee|  PDB=3fee  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3fee FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fee OCA], [https://pdbe.org/3fee PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fee RCSB], [https://www.ebi.ac.uk/pdbsum/3fee PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fee ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NALD2_HUMAN NALD2_HUMAN] Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivate the peptide neurotransmitter N-acetylaspartylglutamate.<ref>PMID:10085079</ref>
+== 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/fe/3fee_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=3fee ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Glutamate carboxypeptidase III (GCPIII) is a metalloenzyme that belongs to the transferrin receptor/glutamate carboxypeptidase II (GCPII; EC 3.4.17.21) superfamily. GCPIII has been studied mainly because of its evolutionary relationship to GCPII, an enzyme involved in a variety of neuropathologies and malignancies, such as glutamatergic neurotoxicity and prostate cancer. Given the potential functional and pharmacological overlap between GCPIII and GCPII, studies addressing the structural and physiological properties of GCPIII are crucial for obtaining a deeper understanding of the GCPII/GCPIII system. In the present study, we report high-resolution crystal structures of the human GCPIII ectodomain in a 'pseudo-unliganded' state and in a complex with: (a) L-glutamate (a product of hydrolysis); (b) a phosphapeptide transition state mimetic, namely (2S,3'S)-{[(3'-amino-3'-carboxy-propyl)-hydroxyphosphinoyl]methyl}-pentane dioic acid; and (c) quisqualic acid, a glutamate biostere. Our data reveal the overall fold and quaternary arrangement of the GCPIII molecule, define the architecture of the GCPIII substrate-binding cavity, and offer an experimental evidence for the presence of Zn(2+) ions in the bimetallic active site. Furthermore, the structures allow us to detail interactions between the enzyme and its ligands and to characterize the functional flexibility of GCPIII, which is essential for substrate recognition. A comparison of these GCPIII structures with the equivalent GCPII complexes reveals differences in the organization of specificity pockets, in surface charge distribution, and in the occupancy of the co-catalytic zinc sites. The data presented here provide information that should prove to be essential for the structurally-aided design of GCPIII-specific inhibitors and might comprise guidelines for future comparative GCPII/GCPIII studies.
-===The high resolution structure of human glutamate carboxypeptidase III (GCPIII/NAALADase II) in complex with quisqualic acid===
+Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III.,Hlouchova K, Barinka C, Konvalinka J, Lubkowski J FEBS J. 2009 Aug;276(16):4448-62. PMID:19678840<ref>PMID:19678840</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3fee" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-FEE 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=3FEE OCA].
+*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:19678840</ref><references group="xtra"/>
+__TOC__
-[[Category: Glutamate carboxypeptidase II]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Barinka, C.]]
+[[Category: Large Structures]]
-[[Category: Hlouchova, K.]]
+[[Category: Barinka C]]
-[[Category: Lubkowski, J.]]
+[[Category: Hlouchova K]]
-[[Category: Bimetallic active site]]
+[[Category: Lubkowski J]]
-[[Category: Calcium cation]]
-[[Category: Carboxypeptidase]]
-[[Category: Chloride anion]]
-[[Category: Dipeptidase]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Membrane]]
-[[Category: Metal-binding]]
-[[Category: Metallopeptidase]]
-[[Category: Metalloprotease]]
-[[Category: Multifunctional enzyme]]
-[[Category: N-glycosylation]]
-[[Category: Polymorphism]]
-[[Category: Protease]]
-[[Category: Signal-anchor]]
-[[Category: Transmembrane]]
-[[Category: Zinc]]
-[[Category: Zinc ion]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Sep 21 16:49:36 2009''