Muconate cycloisomerase (anti)

 

Enzymes in the muconate cycloisomerase (anti) family catalyse the conversion of cis,cis-muconate to muconolactone, in the beta-ketoadipate pathway. Although the enzymes in this family catalyse the same reaction as those in the muconate cycloisomerase (syn) family, the two families use stereochemically distinct mechanisms, and may have evolved independently within the Enolase Superfamily.

 

Reference Protein and Structure

Sequence
A0QTN8 UniProt IPR029065 (Sequence Homologues) (PDB Homologues)
Biological species
Mycobacterium smegmatis str. MC2 155 (Bacteria) Uniprot
PDB
3dg6 - Crystal structure of muconate lactonizing enzyme from Mucobacterium Smegmatis complexed with muconolactone (1.6 Å) PDBe PDBsum 3dg6
Catalytic CATH Domains
3.20.20.120 CATHdb (see all for 3dg6)
Cofactors
Magnesium(2+) (1)
Click To Show Structure

Enzyme Reaction (EC:5.5.1.1)

cis,cis-muconate
CHEBI:32379ChEBI
+
hydron
CHEBI:15378ChEBI
→
(S)-5-oxo-2,5-dihydro-2-furylacetate
CHEBI:58736ChEBI
Alternative enzyme names: 4-carboxymethyl-4-hydroxyisocrotonolactone lyase (decyclizing), Cis,cis-muconate cycloisomerase, Cis,cis-muconate-lactonizing enzyme, Muconate cycloisomerase I, Muconate lactonizing enzyme, Cis,cis-muconate lactonizing enzyme I, CatB, MCl, 2,5-dihydro-5-oxofuran-2-acetate lyase (decyclizing),

Enzyme Mechanism

Introduction

The mechanism is thought to be broadly similar to the syn muconate cycloisomerase (M269): (1) addition of the distal carboxylate to the same face of the proximal double bond to form the enolate intermediate that is stabilised by coordination to the essential Mg(II) as well as proximity to the Lys at the end of the sixth beta-strand. (2) protonation of the intermediate, albeit on opposite faces, by the conserved Lys acid catalyst at the end of the second beta-strand as the result of the differing binding geometries for the cis,cis-muconate substrate.

Catalytic Residues Roles

UniProt PDB* (3dg6)
Asp191, Glu217, Asp242 Asp191A, Glu217A, Asp242A Forms part of the magnesium binding site. metal ligand
Gln294, Lys266 Gln294A, Lys266A Helps stabilise the reactive intermediate and transition states formed during the course of the reaction. electrostatic stabiliser
*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. Sakai A et al. (2009), Biochemistry, 48, 1445-1453. Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families ofcis,cis-Muconate Lactonizing Enzymes†‡. DOI:10.1021/bi802277h. PMID:19220063.
  2. Somboon T et al. (2012), J Mol Model, 18, 525-531. Insight into the reaction mechanism of cis,cis-muconate lactonizing enzymes: a DFT QM/MM study. DOI:10.1007/s00894-011-1088-2. PMID:21541743.

Step 1.

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Catalytic Residues Roles

Residue Roles
Asp191A metal ligand
Glu217A metal ligand
Asp242A metal ligand
Lys162A proton shuttle (general acid/base)
Lys266A electrostatic stabiliser
Gln294A electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Gemma L. Holliday