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| | <StructureSection load='3ff3' size='340' side='right'caption='[[3ff3]], [[Resolution|resolution]] 1.37Å' scene=''> | | <StructureSection load='3ff3' size='340' side='right'caption='[[3ff3]], [[Resolution|resolution]] 1.37Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ff3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FF3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ff3]] 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=3FF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FF3 FirstGlance]. <br> |
| - | </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=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.37Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3fec|3fec]], [[3fed|3fed]], [[3fee|3fee]]</div></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=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAALAD2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glutamate_carboxypeptidase_II Glutamate carboxypeptidase II], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.21 3.4.17.21] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ff3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ff3 OCA], [https://pdbe.org/3ff3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ff3 RCSB], [https://www.ebi.ac.uk/pdbsum/3ff3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ff3 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ff3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ff3 OCA], [https://pdbe.org/3ff3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ff3 RCSB], [https://www.ebi.ac.uk/pdbsum/3ff3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ff3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutamate carboxypeptidase II]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Barinka, C]] | + | [[Category: Barinka C]] |
| - | [[Category: Lubkowski, J]] | + | [[Category: Lubkowski J]] |
| - | [[Category: Bimetallic active site]]
| + | |
| - | [[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: Protease]]
| + | |
| - | [[Category: Signal-anchor]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Zinc ion]]
| + | |
| Structural highlights
3ff3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.37Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pangalos MN, Neefs JM, Somers M, Verhasselt P, Bekkers M, van der Helm L, Fraiponts E, Ashton D, Gordon RD. Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity. J Biol Chem. 1999 Mar 26;274(13):8470-83. PMID:10085079
- ↑ Hlouchova K, Barinka C, Konvalinka J, Lubkowski J. Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III. FEBS J. 2009 Aug;276(16):4448-62. PMID:19678840 doi:10.1111/j.1742-4658.2009.07152.x
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