4p4e - Revision history

OCA at 03:24, 21 November 2024

2024-11-21T03:24:53Z

← Older revision		Revision as of 03:24, 21 November 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4p4e]] 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=4P4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4p4e]] 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=4P4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P4E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2G4:N-[(S)-HYDROXY(4-PHENYLBUTOXY)PHOSPHORYL]-L-GLUTAMIC+ACID'>2G4</scene>, <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=FUC:ALPHA-L-FUCOSE'>FUC</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>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.67Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2G4:N-[(S)-HYDROXY(4-PHENYLBUTOXY)PHOSPHORYL]-L-GLUTAMIC+ACID'>2G4</scene>, <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=FUC:ALPHA-L-FUCOSE'>FUC</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4p4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4e OCA], [https://pdbe.org/4p4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p4e RCSB], [https://www.ebi.ac.uk/pdbsum/4p4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4e 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=4p4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4e OCA], [https://pdbe.org/4p4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p4e RCSB], [https://www.ebi.ac.uk/pdbsum/4p4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4e ProSAT]</span></td></tr>
	</table>		</table>

OCA at 12:41, 1 February 2023

2023-02-01T12:41:25Z

← Older revision		Revision as of 12:41, 1 February 2023
Line 3:		Line 3:
	<StructureSection load='4p4e' size='340' side='right'caption='[[4p4e]], [[Resolution\|resolution]] 1.67Å' scene=''>		<StructureSection load='4p4e' size='340' side='right'caption='[[4p4e]], [[Resolution\|resolution]] 1.67Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4p4e]] 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=4P4E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4P4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4p4e]] 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=4P4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P4E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2G4:N-[(S)-HYDROXY(4-PHENYLBUTOXY)PHOSPHORYL]-L-GLUTAMIC+ACID'>2G4</scene>, <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=FUC:ALPHA-L-FUCOSE'>FUC</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>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2G4:N-[(S)-HYDROXY(4-PHENYLBUTOXY)PHOSPHORYL]-L-GLUTAMIC+ACID'>2G4</scene>, <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=FUC:ALPHA-L-FUCOSE'>FUC</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4b\|4p4b]], [[4p4d\|4p4d]], [[4p4f\|4p4f]], [[4p4i\|4p4i]], [[4p4j\|4p4j]]</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=4p4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4e OCA], [https://pdbe.org/4p4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p4e RCSB], [https://www.ebi.ac.uk/pdbsum/4p4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4e ProSAT]</span></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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4p4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4e OCA], [~~http~~://pdbe.org/4p4e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4p4e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4p4e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4e 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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	==See Also==		==See Also==
	*[[Carboxypeptidase\|Carboxypeptidase]]		*[[Carboxypeptidase 3D structures\|Carboxypeptidase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__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: Hydrolase]]~~
	~~[[Category: Naaladase]]~~
	~~[[Category: Phosphoramidate]]~~
	~~[[Category: Prostate-specific membrane antigen~~]]

OCA at 08:22, 17 April 2019

2019-04-17T08:22:00Z

← Older revision		Revision as of 08:22, 17 April 2019
Line 1:		Line 1:

	==X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a phosphoramidate inhibitor MP1D==		==X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a phosphoramidate inhibitor MP1D==
	<StructureSection load='4p4e' size='340' side='right' caption='[[4p4e]], [[Resolution\|resolution]] 1.67Å' scene=''>		<StructureSection load='4p4e' size='340' side='right'caption='[[4p4e]], [[Resolution\|resolution]] 1.67Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4p4e]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4p4e]] 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=4P4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P4E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2G4:N-[(S)-HYDROXY(4-PHENYLBUTOXY)PHOSPHORYL]-L-GLUTAMIC+ACID'>2G4</scene>, <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=FUC:ALPHA-L-FUCOSE'>FUC</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>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2G4:N-[(S)-HYDROXY(4-PHENYLBUTOXY)PHOSPHORYL]-L-GLUTAMIC+ACID'>2G4</scene>, <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=FUC:ALPHA-L-FUCOSE'>FUC</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4b\|4p4b]], [[4p4d\|4p4d]], [[4p4f\|4p4f]], [[4p4i\|4p4i]], [[4p4j\|4p4j]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4b\|4p4b]], [[4p4d\|4p4d]], [[4p4f\|4p4f]], [[4p4i\|4p4i]], [[4p4j\|4p4j]]</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='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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4e OCA], [http://pdbe.org/4p4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p4e RCSB], [http://www.ebi.ac.uk/pdbsum/4p4e PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4e OCA], [http://pdbe.org/4p4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p4e RCSB], [http://www.ebi.ac.uk/pdbsum/4p4e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4p4e" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4p4e" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Carboxypeptidase\|Carboxypeptidase]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Glutamate carboxypeptidase II]]		[[Category: Glutamate carboxypeptidase II]]
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Barinka, C]]		[[Category: Barinka, C]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 22:19, 30 November 2015

2015-11-30T22:19:51Z

← Older revision		Revision as of 22:19, 30 November 2015
Line 6:		Line 6:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4b\|4p4b]], [[4p4d\|4p4d]], [[4p4f\|4p4f]], [[4p4i\|4p4i]], [[4p4j\|4p4j]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4b\|4p4b]], [[4p4d\|4p4d]], [[4p4f\|4p4f]], [[4p4i\|4p4i]], [[4p4j\|4p4j]]</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='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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p4e RCSB], [http://www.ebi.ac.uk/pdbsum/4p4e PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4e OCA], [http://pdbe.org/4p4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p4e RCSB], [http://www.ebi.ac.uk/pdbsum/4p4e PDBsum]</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.		[[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 ==
			Inhibitors targeting human glutamate carboxypeptidase II (GCPII) typically consist of a P1' glutamate-derived binding module, which warrants the high affinity and specificity, linked to an effector function that is positioned within the entrance funnel of the enzyme. Here we present a comprehensive structural and computational study aimed at dissecting the importance of the effector function for GCPII binding and affinity. To this end we determined crystal structures of human GCPII in complex with a series of phosphoramidate-based inhibitors harboring effector functions of diverse physicochemical characteristics. Our data show that higher binding affinities of phosphoramidates, compared to matching phosphonates, are linked to the presence of additional hydrogen bonds between Glu424 and Gly518 of the enzyme and the amide group of the phosphoramidate. While the positioning of the P1' glutamate-derived module within the S1' pocket of GCPII is invariant, interaction interfaces between effector functions and residues lining the entrance funnel are highly varied, with the positively charged arginine patch defined by Arg463, Arg534 and Arg536 being the only 'hot-spot' common to several studied complexes. This variability stems in part from the fact that the effector/GCPII interfaces generally encompass isolated areas of nonpolar residues within the entrance funnel and resulting van der Waals contacts lack the directionality typical for hydrogen bonding interactions. The presented data unravel a complexity of binding modes of inhibitors within non-prime site(s) of GCPII and can be exploited for the design of novel GCPII-specific compounds. PDB ID CODES: Atomic coordinates of the present structures together with the experimental structure factor amplitudes were deposited at the RCSB Protein Data Bank under accession codes 4P44 (complex with JRB-4-81), 4P45 (complex with JRB-4-73), 4P4B (complex with CTT54), 4P4D (complex with MP1C), 4P4E (complex with MP1D), 4P4F (complex with NC-2-40), 4P4I (complex with T33) and 4P4J (complex with T33D).

			Design of composite inhibitors targeting glutamate carboxypeptidase II: the importance of effector functionalities.,Novakova Z, Cerny J, Choy CJ, R Nedrow J, Choi JK, Lubkowski J, Berkman CE, Barinka C FEBS J. 2015 Oct 13. doi: 10.1111/febs.13557. PMID:26460595<ref>PMID:26460595</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4p4e" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 12:15, 20 May 2015

2015-05-20T12:15:52Z

← Older revision		Revision as of 12:15, 20 May 2015
Line 1:		Line 1:
	'''~~Unreleased structure~~'''		==X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a phosphoramidate inhibitor MP1D==
			<StructureSection load='4p4e' size='340' side='right' caption='[[4p4e]], [[Resolution\|resolution]] 1.67Å' scene=''>
	~~The entry~~ 4p4e is ~~ON HOLD~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4p4e]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P4E FirstGlance]. <br>
	~~Authors~~: ~~Barinka~~, C.		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2G4:N-[(S)-HYDROXY(4-PHENYLBUTOXY)PHOSPHORYL]-L-GLUTAMIC+ACID'>2G4</scene>, <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=FUC:ALPHA-L-FUCOSE'>FUC</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4b\|4p4b]], [[4p4d\|4p4d]], [[4p4f\|4p4f]], [[4p4i\|4p4i]], [[4p4j\|4p4j]]</td></tr>
	~~Description~~: X-~~ray structure~~ of ~~human glutamate carboxypeptidase II~~ (~~GCPII~~) in ~~complex with~~ a ~~phosphoramidate inhibitor MP1D~~		<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>
	[[Category: ~~Unreleased Structures~~]]		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p4e RCSB], [http://www.ebi.ac.uk/pdbsum/4p4e PDBsum]</span></td></tr>
			</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.
			__TOC__
			</StructureSection>
			[[Category: Glutamate carboxypeptidase II]]
	[[Category: Barinka, C]]		[[Category: Barinka, C]]
			[[Category: Hydrolase]]
			[[Category: Naaladase]]
			[[Category: Phosphoramidate]]
			[[Category: Prostate-specific membrane antigen]]

OCA at 14:46, 24 December 2014

2014-12-24T14:46:06Z

← Older revision		Revision as of 14:46, 24 December 2014
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	Description: X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a phosphoramidate inhibitor MP1D		Description: X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a phosphoramidate inhibitor MP1D
			[[Category: Unreleased Structures]]
			[[Category: Barinka, C]]

OCA: Protected "4p4e" [edit=sysop:move=sysop]

2014-03-19T07:34:26Z

Protected "4p4e" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:34, 19 March 2014
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4p4e is ON HOLD Authors: Barinka, C. Description: X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a phosphoramidate ...

2014-03-19T07:34:25Z

New page: '''Unreleased structure''' The entry 4p4e is ON HOLD Authors: Barinka, C. Description: X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a phosphoramidate ...

New page

'''Unreleased structure'''

The entry 4p4e is ON HOLD

Authors: Barinka, C.

Description: X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a phosphoramidate inhibitor MP1D