3d7d: Difference between revisions

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[[Image:3d7d.png|left|200px]]
==A high resolution crystal structure of human glutamate carboxypeptidase II (GCPII) in a complex with DCFBD, a urea-based inhibitor==
<StructureSection load='3d7d' size='340' side='right' caption='[[3d7d]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3d7d]] 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=3D7D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3D7D FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=FBD:N-({(1R)-1-CARBOXY-2-[(4-FLUOROBENZYL)SULFANYL]ETHYL}CARBAMOYL)-L-GLUTAMIC+ACID'>FBD</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><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3d7f|3d7f]], [[3d7g|3d7g]], [[3d7h|3d7h]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FOLH1, FOLH, NAALAD1, PSM, PSMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3d7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d7d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3d7d RCSB], [http://www.ebi.ac.uk/pdbsum/3d7d PDBsum]</span></td></tr>
<table>
== 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/d7/3d7d_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Urea-based, low molecular weight ligands of glutamate carboxypeptidase II (GCPII) have demonstrated efficacy in various models of neurological disorders and can serve as imaging agents for prostate cancer. To enhance further development of such compounds, we determined X-ray structures of four complexes between human GCPII and urea-based inhibitors at high resolution. All ligands demonstrate an invariant glutarate moiety within the S1' pocket of the enzyme. The ureido linkage between P1 and P1' inhibitor sites interacts with the active-site Zn(1)(2+) ion and the side chains of Tyr552 and His553. Interactions within the S1 pocket are defined primarily by a network of hydrogen bonds between the P1 carboxylate group of the inhibitors and the side chains of Arg534, Arg536, and Asn519. Importantly, we have identified a hydrophobic pocket accessory to the S1 site that can be exploited for structure-based design of novel GCPII inhibitors with increased lipophilicity.


{{STRUCTURE_3d7d|  PDB=3d7d  |  SCENE=  }}
Interactions between human glutamate carboxypeptidase II and urea-based inhibitors: structural characterization.,Barinka C, Byun Y, Dusich CL, Banerjee SR, Chen Y, Castanares M, Kozikowski AP, Mease RC, Pomper MG, Lubkowski J J Med Chem. 2008 Dec 25;51(24):7737-43. PMID:19053759<ref>PMID:19053759</ref>


===A high resolution crystal structure of human glutamate carboxypeptidase II (GCPII) in a complex with DCFBD, a urea-based inhibitor===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_19053759}}
 
==About this Structure==
[[3d7d]] 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=3D7D OCA].


==See Also==
==See Also==
*[[Carboxypeptidase|Carboxypeptidase]]
*[[Carboxypeptidase|Carboxypeptidase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:019053759</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Glutamate carboxypeptidase II]]
[[Category: Glutamate carboxypeptidase II]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]

Revision as of 11:33, 29 September 2014

A high resolution crystal structure of human glutamate carboxypeptidase II (GCPII) in a complex with DCFBD, a urea-based inhibitorA high resolution crystal structure of human glutamate carboxypeptidase II (GCPII) in a complex with DCFBD, a urea-based inhibitor

Structural highlights

3d7d 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.
Ligands:, , , , , ,
Related:3d7f, 3d7g, 3d7h
Gene:FOLH1, FOLH, NAALAD1, PSM, PSMA (Homo sapiens)
Activity:Glutamate carboxypeptidase II, with EC number 3.4.17.21
Resources:FirstGlance, OCA, RCSB, PDBsum

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

Urea-based, low molecular weight ligands of glutamate carboxypeptidase II (GCPII) have demonstrated efficacy in various models of neurological disorders and can serve as imaging agents for prostate cancer. To enhance further development of such compounds, we determined X-ray structures of four complexes between human GCPII and urea-based inhibitors at high resolution. All ligands demonstrate an invariant glutarate moiety within the S1' pocket of the enzyme. The ureido linkage between P1 and P1' inhibitor sites interacts with the active-site Zn(1)(2+) ion and the side chains of Tyr552 and His553. Interactions within the S1 pocket are defined primarily by a network of hydrogen bonds between the P1 carboxylate group of the inhibitors and the side chains of Arg534, Arg536, and Asn519. Importantly, we have identified a hydrophobic pocket accessory to the S1 site that can be exploited for structure-based design of novel GCPII inhibitors with increased lipophilicity.

Interactions between human glutamate carboxypeptidase II and urea-based inhibitors: structural characterization.,Barinka C, Byun Y, Dusich CL, Banerjee SR, Chen Y, Castanares M, Kozikowski AP, Mease RC, Pomper MG, Lubkowski J J Med Chem. 2008 Dec 25;51(24):7737-43. PMID:19053759[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Barinka C, Byun Y, Dusich CL, Banerjee SR, Chen Y, Castanares M, Kozikowski AP, Mease RC, Pomper MG, Lubkowski J. Interactions between human glutamate carboxypeptidase II and urea-based inhibitors: structural characterization. J Med Chem. 2008 Dec 25;51(24):7737-43. PMID:19053759 doi:10.1021/jm800765e

3d7d, resolution 1.69Å

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