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| | {{STRUCTURE_1cg2| PDB=1cg2 | SCENE= }} | | {{STRUCTURE_1cg2| PDB=1cg2 | SCENE= }} |
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| - | '''CARBOXYPEPTIDASE G2'''
| + | ===CARBOXYPEPTIDASE G2=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9083113}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9083113 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9083113}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| | [[Category: Metallocarboxypeptidase]] | | [[Category: Metallocarboxypeptidase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 12:41:52 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 20:42:09 2008'' |
Revision as of 17:42, 30 June 2008
Template:STRUCTURE 1cg2
CARBOXYPEPTIDASE G2
Template:ABSTRACT PUBMED 9083113
About this Structure
1CG2 is a Single protein structure of sequence from Pseudomonas sp.. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Jun 30 20:42:09 2008
