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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1avq
Original Entry
Title:
Deoxyribonuclease
Compound:
Lambda exonuclease
Mutant:
Yes
UniProt/Swiss-Prot:
P03697-EXO_LAMBD
EC Class:
3.1.11.3
Other CSA Entries:
Overview of all sites for 1avq
Homologues of 1avq
Entries for UniProt/Swiss-Prot: P03697
Entries for EC: 3.1.11.3
Other Databases:
PDB entry: 1avq
PDBsum entry: 1avq
UniProt/Swiss-Prot: P03697
IntEnz entry: 3.1.11.3
Literature Report:
Introduction:
Lambda-exonuclease from Bacteriophage lambda is a 5'->3' exonuclease. It catalyses the hydrolysis of one strand of double stranded DNA in a 5' to 3' direction, leaving single stranded DNA. This is involved in DNA replication, recombination and repair. Once started on a reaction, lambda-exonuclease will continue to hydrolyse until either the DNA strand ends, or the enzyme dissociates into monomers.
Mechanism:
The three-metal mechanism of EcoRV is the most likely mechanism for lambda-exonuclease.

1. Metal I and Lys 131 between them activate a water molecule for nucleophilic attack on the scissile phosphate.
2. Nucleophilic attack creates a negatively charged, penta-coordinate transition state, which is stabilised by metal III.
3. The 3' O atom of the leaving group of the SN2 reaction is protonated by a water molecule. The resulting hydroxide is stabilised by metal III.
Sites:

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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
LYSA 131 131Sidechain
ElectrostaticWater
Activates a water molecule for nucleophilic attack on the scissile phosphate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10508668 Current protein Conservation of residue
PubMed ID 10508668 Current protein Mutagenesis of residue
PubMed ID 10508668 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 10508668 Current protein Structural similarity to homologue of known mechanism
Notes:
The mechanism proposed here is based purely on lambda-exonuclease's homology to EcoRV (stated in 9653111.) Metals I, II and III are not in the crystallised structure of lambda-exonuclease 1avq. Residues Asp 119 and Glu 129 are stated to be catalytic, but seem to only be necessary for binding.
References:
1
Type II restriction endonucleases: structural, functional and evolutionary relationships.
R. A. Kovall and B. W. Matthews
Curr Opin Chem Biol 3, (5) 578-83, (1999).
10508668
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