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[[Image:1cg2.jpg|left|200px]]<br /><applet load="1cg2" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1cg2, resolution 2.5&Aring;" />
'''CARBOXYPEPTIDASE G2'''<br />


==Overview==
==CARBOXYPEPTIDASE G2==
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.
<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 [https://en.wikipedia.org/wiki/Pseudomonas_sp._RS-16 Pseudomonas sp. RS-16]. 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 [https://proteopedia.org/fgij/fg.htm?mol=1CG2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=1cg2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cg2 OCA], [https://pdbe.org/1cg2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cg2 RCSB], [https://www.ebi.ac.uk/pdbsum/1cg2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cg2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://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].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1CG2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_sp. Pseudomonas sp.] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Known structural/functional Sites: <scene name='pdbsite=CTA:Catalytic+Site'>CTA</scene>, <scene name='pdbsite=CTB:Catalytic+Site'>CTB</scene>, <scene name='pdbsite=CTC:Catalytic+Site'>CTC</scene> and <scene name='pdbsite=CTD:Catalytic+Site'>CTD</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CG2 OCA].
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9083113 9083113]
[[Category: Large Structures]]
[[Category: Glutamate carboxypeptidase]]
[[Category: Pseudomonas sp. RS-16]]
[[Category: Pseudomonas sp.]]
[[Category: Blow DM]]
[[Category: Single protein]]
[[Category: Brick P]]
[[Category: Blow, D.M.]]
[[Category: Melton RG]]
[[Category: Brick, P.]]
[[Category: Pauptit RA]]
[[Category: Melton, R.G.]]
[[Category: Rowsell S]]
[[Category: Pauptit, R.A.]]
[[Category: Tucker AD]]
[[Category: Rowsell, S.]]
[[Category: Tucker, A.D.]]
[[Category: ZN]]
[[Category: hydrolase]]
[[Category: metallocarboxypeptidase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:34:37 2008''

Latest revision as of 10:24, 14 February 2024

CARBOXYPEPTIDASE G2CARBOXYPEPTIDASE G2

Structural highlights

1cg2 is a 4 chain structure with sequence from Pseudomonas sp. RS-16. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CBPG_PSES6 Catalyzes the hydrolysis of reduced and non-reduced folates to pteroates and L-glutamate. This enzyme has a broad specificity.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1cg2, resolution 2.50Å

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