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3sjg

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[[Image:3sjg.png|left|200px]]
 
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==Human glutamate carboxypeptidase II (E424A inactive mutant ) in complex with N-acetyl-aspartyl-aminooctanoic acid==
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The line below this paragraph, containing "STRUCTURE_3sjg", creates the "Structure Box" on the page.
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<StructureSection load='3sjg' size='340' side='right'caption='[[3sjg]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3sjg]] 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=3SJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SJG FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SDR:(2S)-2-[(N-ACETYL-L-ALPHA-ASPARTYL)AMINO]NONANOIC+ACID'>SDR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3sje|3sje]], [[3sjf|3sjf]], [[3sjx|3sjx]]</div></td></tr>
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{{STRUCTURE_3sjg| PDB=3sjg | SCENE= }}
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FOLH, FOLH1, GIG27, NAALAD1, PSM, PSMA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3sjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sjg OCA], [https://pdbe.org/3sjg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sjg RCSB], [https://www.ebi.ac.uk/pdbsum/3sjg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sjg ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Virtually all low molecular weight inhibitors of human glutamate carboxypeptidase II (GCPII) are highly polar compounds that have limited use in settings where more lipophilic molecules are desired. Here we report the identification and characterization of GCPII inhibitors with enhanced liphophilicity that are derived from a series of newly identified dipeptidic GCPII substrates featuring non-polar aliphatic side chains at the C-terminus. To analyze the interactions governing the substrate recognition by GCPII, we determined crystal structures of the inactive GCPII(E424A) mutant in complex with selected dipeptides and complemented the structural data with quantum mechanics/molecular mechanics calculations. Results reveal the importance of non-polar interactions governing GCPII affinity towards novel substrates as well as formerly unnoticed plasticity of the S1' specificity pocket. Based on those data, we designed, synthesized and evaluated a series of novel GCPII inhibitors with enhanced lipophilicity, with the best candidates having low nanomolar inhibition constants and clogD &gt; 0.3. Our findings offer new insights into the design of more lipophilic inhibitors targeting GCPII.
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===Human glutamate carboxypeptidase II (E424A inactive mutant ) in complex with N-acetyl-aspartyl-aminooctanoic acid===
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Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity.,Plechanovova A, Byun Y, Alquicer G, Skultetyova L, Mlcochova P, Nemcova A, Kim HJ, Navratil M, Mease RC, Lubkowski J, Pomper MG, Konvalinka J, Rulisek L, Barinka C J Med Chem. 2011 Sep 19. PMID:21923190<ref>PMID:21923190</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3sjg" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_21923190}}, adds the Publication Abstract to the page
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*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 21923190 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_21923190}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[3sjg]] is a 1 chain structure with 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=3SJG OCA].
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==Reference==
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<ref group="xtra">PMID:021923190</ref><references group="xtra"/>
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[[Category: Glutamate carboxypeptidase II]]
[[Category: Glutamate carboxypeptidase II]]
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[[Category: Homo sapiens]]
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[[Category: Human]]
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[[Category: Alquicer, G.]]
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[[Category: Large Structures]]
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[[Category: Barinka, C.]]
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[[Category: Alquicer, G]]
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[[Category: Byun, Y.]]
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[[Category: Barinka, C]]
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[[Category: Kim, H.]]
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[[Category: Byun, Y]]
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[[Category: Konvalinka, J.]]
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[[Category: Kim, H]]
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[[Category: Lubkowski, J.]]
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[[Category: Konvalinka, J]]
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[[Category: Mease, R.]]
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[[Category: Lubkowski, J]]
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[[Category: Mlcochova, P.]]
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[[Category: Mease, R]]
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[[Category: Navratil, M.]]
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[[Category: Mlcochova, P]]
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[[Category: Nemcova, A.]]
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[[Category: Navratil, M]]
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[[Category: Plechanovova, A.]]
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[[Category: Nemcova, A]]
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[[Category: Pomper, M.]]
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[[Category: Plechanovova, A]]
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[[Category: Rulisek, L.]]
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[[Category: Pomper, M]]
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[[Category: Skultetyova, L.]]
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[[Category: Rulisek, L]]
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[[Category: Skultetyova, L]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Metallopeptidase]]
[[Category: Metallopeptidase]]

Current revision

Human glutamate carboxypeptidase II (E424A inactive mutant ) in complex with N-acetyl-aspartyl-aminooctanoic acid

PDB ID 3sjg

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