View source for 1cg2

==CARBOXYPEPTIDASE G2==
<StructureSection load='1cg2' size='340' side='right' caption='[[1cg2]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1cg2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Pses6 Pses6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CG2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CG2 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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 Glutamate carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.11 3.4.17.11] </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=1cg2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cg2 OCA], [http://pdbe.org/1cg2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1cg2 RCSB], [http://www.ebi.ac.uk/pdbsum/1cg2 PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/CBPG_PSES6 CBPG_PSES6]] Catalyzes the hydrolysis of reduced and non-reduced folates to pteroates and L-glutamate. This enzyme has a broad specificity. 
== 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/cg/1cg2_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/main_output.php?pdb_ID=1cg2 ConSurf].
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== Publication Abstract from PubMed ==
BACKGROUND: Carboxypeptidase G enzymes hydrolyze the C-terminal glutamate moiety from folic acid and its analogues, such as methotrexate. The enzyme studied here, carboxypeptidase G2 (CPG2), is a dimeric zinc-dependent exopeptidase produced by Pseudomonas sp. strain RS-16. CPG2 has applications in cancer therapy: following its administration as an immunoconjugate, in which CPG2 is linked to an antibody to a tumour-specific antigen, it can enzymatically convert subsequently administered inactive prodrugs to cytotoxic drugs selectively at the tumour site. CPG2 has no significant amino acid sequence homology with proteins of known structure. Hence, structure determination of CPG2 was undertaken to identify active-site residues, which may in turn provide ideas for protein and/or substrate modification with a view to improving its therapeutic usefulness. RESULTS: We have determined the crystal structure of CPG2 at 2.5 A resolution using multiple isomorphous replacement methods and non-crystallographic symmetry averaging. Each subunit of the molecular dimer consists of a larger catalytic domain containing two zinc ions at the active site, and a separate smaller domain that forms the dimer interface. The two active sites in the dimer are more than 60 A apart and are presumed to be independent; each contains a symmetric distribution of carboxylate and histidine ligands around two zinc ions which are 3.3 A apart. This distance is bridged by two shared zinc ligands, an aspartic acid residue and a hydroxyl ion. CONCLUSIONS: We find that the CPG2 catalytic domain has structural homology with other zinc-dependent exopeptidases, both those with a single zinc ion and those with a pair of zinc ions in the active site. The closest structural homology is with the aminopeptidase from Aeromonas proteolytica, where the similarity includes superposable zinc ligands but does not extend to the rest of the active-site residues, consistent with the different substrate specificities. The mechanism of peptide cleavage is likely to be very similar in these two enzymes and may involve the bridging hydroxyl ion ligand acting as a primary nucleophile.

Crystal structure of carboxypeptidase G2, a bacterial enzyme with applications in cancer therapy.,Rowsell S, Pauptit RA, Tucker AD, Melton RG, Blow DM, Brick P Structure. 1997 Mar 15;5(3):337-47. PMID:9083113<ref>PMID:9083113</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1cg2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carboxypeptidase|Carboxypeptidase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Glutamate carboxypeptidase]]
[[Category: Pses6]]
[[Category: Blow, D M]]
[[Category: Brick, P]]
[[Category: Melton, R G]]
[[Category: Pauptit, R A]]
[[Category: Rowsell, S]]
[[Category: Tucker, A D]]
[[Category: Hydrolase]]
[[Category: Metallocarboxypeptidase]]