N-succinylamino acid racemase (type 2)

 

Enzymes in the N-succinylamino acid racemase 2 (NSAR2) family catalyse the racemisation of N-succinyl arginine/lysine. Enzymes in this family are highly similar to enzymes in the dipeptide epimerase family. The experimentally characterised enzyme from Bacillus cereus has been shown to catalyse the epimerisation of certain dipeptides, but at a substantially lower rate than the racemisation of N-succinyl arginine/lysine. Although the reaction catalysed by this family is similar to that catalysed by the NSAR family (differing only in the preference of N-succinyl arginine/lysine for NSAR2 versus N-succinyl hydrophobic amino acids for NSAR), phylogenetic analysis suggests that these two families have independent evolutionary origins within the enolase superfamily. Not surprisingly, the amino acids responsible for substrate recognition appear to differ between the two families.

 

Reference Protein and Structure

Sequence
Q81IL5 UniProt (5.1.1.-) IPR034390 (Sequence Homologues) (PDB Homologues)
Biological species
Bacillus cereus ATCC 14579 (Bacteria) Uniprot
PDB
2p8b - Crystal structure of N-succinyl Arg/Lys racemase from Bacillus cereus ATCC 14579 complexed with N-succinyl Lys. (1.7 Å) PDBe PDBsum 2p8b
Catalytic CATH Domains
3.20.20.120 CATHdb (see all for 2p8b)
Cofactors
Magnesium(2+) (1)
Click To Show Structure

Enzyme Reaction (EC:5.1.1.-)

N-succinyl-L-amino acid residue
CHEBI:85535ChEBI
→
N-succinyl-D-amino acid
CHEBI:85536ChEBI

Enzyme Mechanism

Introduction

Thought to proceed via a two-base 1,1-proton transfer mechanism highly similar to other reactions in this subgroup of Enolase Superfamily members, which includes NSAR, MLE and dipeptide epimerases. The general acid/bases are proposed to be two lysine residues that reside on opposite sides of the substrate.

Catalytic Residues Roles

UniProt PDB* (2p8b)
Asp191, Glu218, Asp243 Asp191A, Glu218A, Asp243A Forms part of the magnesium binding site. metal ligand
Lys163, Lys267 Lys163A, Lys267A Proposed to act as the general acid/bases during the course of the reaction. Depending on the direction of the epimerisation, one of the lysine residues abstracts the alpha proton, the other acts as the general acid that reprotonates the alpha carbon to produce the opposite stereoisomer. proton shuttle (general acid/base)
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Song L et al. (2007), Nat Chem Biol, 3, 486-491. Prediction and assignment of function for a divergent N-succinyl amino acid racemase. DOI:10.1038/nchembio.2007.11. PMID:17603539.

Step 1.

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Catalytic Residues Roles

Residue Roles
Lys163A proton shuttle (general acid/base)
Lys267A proton shuttle (general acid/base)
Asp191A metal ligand
Glu218A metal ligand
Asp243A metal ligand

Chemical Components

Step 1.

Contributors

Gemma L. Holliday