6rbc - Revision history

OCA at 12:18, 24 January 2024

2024-01-24T12:18:32Z

←Older revision		Revision as of 12:18, 24 January 2024
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	<StructureSection load='6rbc' size='340' side='right'caption='[[6rbc]], [[Resolution\|resolution]] 1.77Å' scene=''>		<StructureSection load='6rbc' size='340' side='right'caption='[[6rbc]], [[Resolution\|resolution]] 1.77Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6rbc]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RBC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6RBC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6rbc]] 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=6RBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RBC FirstGlance]. <br>
-	</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=JX5:(2~{S})-2-[[(2~{R})-2-[4-[(4-iodophenyl)carbonylamino]butanoylamino]-3-oxidanyl-3-oxidanylidene-propyl]carbamoylamino]pentanedioic+acid'>JX5</scene>, <scene name='pdbligand=~~NAG~~:~~N-ACETYL~~-D-~~GLUCOSAMINE~~'>~~NAG~~</scene>, <scene name='pdbligand=ZN:~~ZINC+ION~~'>ZN</scene>, <scene name='pdbligand=~~MAN~~:~~ALPHA-D-MANNOSE~~'>~~MAN~~</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]] 1.77Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FOLH1, FOLH, NAALAD1, PSM, PSMA, GIG27 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=JX5:(2~{S})-2-[[(2~{R})-2-[4-[(4-iodophenyl)carbonylamino]butanoylamino]-3-oxidanyl-3-oxidanylidene-propyl]carbamoylamino]pentanedioic+acid'>JX5</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>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=6rbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rbc OCA], [https://pdbe.org/6rbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rbc RCSB], [https://www.ebi.ac.uk/pdbsum/6rbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rbc ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6rbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rbc OCA], [~~http~~://pdbe.org/6rbc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6rbc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6rbc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6rbc ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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.	+	[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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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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: Kutil, Z]]	+	[[Category: Kutil Z]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Naaladase]]~~	+
-	~~[[Category: Prostate-specific membrane antigen]]~~	+
-	~~[[Category: Urea-based inhibitor~~]]	+

OCA at 07:06, 25 November 2020

2020-11-25T07:06:36Z

←Older revision		Revision as of 07:06, 25 November 2020
Line 1:		Line 1:

	==X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a inhibitor KB1157==		==X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a inhibitor KB1157==
-	<StructureSection load='6rbc' size='340' side='right'caption='[[6rbc]]' scene=''>	+	<StructureSection load='6rbc' size='340' side='right'caption='[[6rbc]], [[Resolution\|resolution]] 1.77Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RBC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RBC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6rbc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RBC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RBC FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rbc OCA], [http://pdbe.org/6rbc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rbc RCSB], [http://www.ebi.ac.uk/pdbsum/6rbc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rbc ProSAT]</span></td></tr>	+	</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=JX5:(2~{S})-2-[[(2~{R})-2-[4-[(4-iodophenyl)carbonylamino]butanoylamino]-3-oxidanyl-3-oxidanylidene-propyl]carbamoylamino]pentanedioic+acid'>JX5</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FOLH1, FOLH, NAALAD1, PSM, PSMA, GIG27 ([http://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'>[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] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rbc OCA], [http://pdbe.org/6rbc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rbc RCSB], [http://www.ebi.ac.uk/pdbsum/6rbc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rbc ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys-urea-Glu motif, in which Lys and Glu are alpha-(l)-amino acids. In this study, we aimed to determine the effect of beta- and gamma-amino acids in the S1 pocket on the binding affinity for PSMA. We synthesized and evaluated the beta- and gamma-amino acid analogues with (S)- or (R)-configuration with keeping alpha-(l)-Glu as the S1'-binding pharmacophore. The structure-activity relationship studies identified that compound 13c, a beta-amino acid analogue with (R)-configuration, exhibited the most potent PSMA inhibitory activity with an IC50 value of 3.97 nM. The X-ray crystal structure of PSMA in complex with 13c provided a mechanistic basis for the stereochemical preference of PSMA, which can guide the development of future PSMA inhibitors.
		+
		+	Novel beta- and gamma-Amino Acid-Derived Inhibitors of Prostate-Specific Membrane Antigen.,Kim K, Kwon H, Barinka C, Motlova L, Nam S, Choi D, Ha H, Nam H, Son SH, Minn I, Pomper MG, Yang X, Kutil Z, Byun Y J Med Chem. 2020 Mar 26;63(6):3261-3273. doi: 10.1021/acs.jmedchem.9b02022. Epub , 2020 Mar 9. PMID:32097010<ref>PMID:32097010</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6rbc" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Carboxypeptidase 3D structures\|Carboxypeptidase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Glutamate carboxypeptidase II]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Barinka C]]	+	[[Category: Barinka, C]]
-	[[Category: Kutil Z]]	+	[[Category: Kutil, Z]]
		+	[[Category: Hydrolase]]
		+	[[Category: Naaladase]]
		+	[[Category: Prostate-specific membrane antigen]]
		+	[[Category: Urea-based inhibitor]]

OCA at 05:27, 13 May 2020

2020-05-13T05:27:58Z

←Older revision		Revision as of 05:27, 13 May 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6rbc is ON HOLD until Paper Publication~~	+	==X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a inhibitor KB1157==
-		+	<StructureSection load='6rbc' size='340' side='right'caption='[[6rbc]]' scene=''>
-	~~Authors: Barinka, C., Kutil, Z.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RBC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RBC FirstGlance]. <br>
-	~~Description:~~ X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a inhibitor KB1157	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rbc OCA], [http://pdbe.org/6rbc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rbc RCSB], [http://www.ebi.ac.uk/pdbsum/6rbc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rbc ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Barinka, C]]	+	__TOC__
-	[[Category: Kutil, Z]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Barinka C]]
		+	[[Category: Kutil Z]]

OCA at 07:20, 1 May 2019

2019-05-01T07:20:35Z

←Older revision		Revision as of 07:20, 1 May 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6rbc is ON HOLD	+	The entry 6rbc is ON HOLD until Paper Publication

	Authors: Barinka, C., Kutil, Z.		Authors: Barinka, C., Kutil, Z.

OCA: Protected "6rbc" [edit=sysop:move=sysop]

2019-04-17T04:24:23Z

Protected "6rbc" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:24, 17 April 2019

OCA: New page: '''Unreleased structure''' The entry 6rbc is ON HOLD Authors: Barinka, C., Kutil, Z. Description: X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a inhib...

2019-04-17T04:24:22Z

New page: '''Unreleased structure''' The entry 6rbc is ON HOLD Authors: Barinka, C., Kutil, Z. Description: X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a inhib...

New page

'''Unreleased structure'''

The entry 6rbc is ON HOLD

Authors: Barinka, C., Kutil, Z.

Description: X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a inhibitor KB1157
[[Category: Unreleased Structures]]
[[Category: Barinka, C]]
[[Category: Kutil, Z]]