Precorrin-8X methylmutase

 

Precorrin-8x methyl mutase (CobH) catalyses the migration of a methyl group attached to C-11 of the substrate, precorrin-8x, to the adjacent C-12 to give the product hydrogenobyrinic acid (HBA).This is a step in the aerobic biosynthesis of the corrin macrocycle of vitamin B12.

 

Reference Protein and Structure

Sequence
P21638 UniProt (5.4.99.61) IPR003722 (Sequence Homologues) (PDB Homologues)
Biological species
Sinorhizobium sp. Uniprot
PDB
1f2v - CRYSTAL STRUCTURE ANALYSIS OF PRECORRIN-8X METHYLMUTASE OF AEROBIC VITAMIN B12 SYNTHESIS (2.1 Å) PDBe PDBsum 1f2v
Catalytic CATH Domains
3.40.50.10230 CATHdb (see all for 1f2v)
Click To Show Structure

Enzyme Reaction (EC:5.4.99.61)

precorrin-8X(7-)
CHEBI:58581ChEBI
→
hydrogenobyrinate(4-)
CHEBI:77873ChEBI
Alternative enzyme names: Hydrogenobyrinic acid-binding protein, Precorrin isomerase, HBA synthase, CobH (gene name),

Enzyme Mechanism

Introduction

CobH is one of a few known enzymes that catalyse pericyclic reactions. His 43 protonates the nitrogen of the pyrrolenine C ring of precorrin-8x, which triggers a suprafacial [1,5]-sigmatropic rearrangement; the methyl group passes from C-11 to C-12 in a single concerted step, with the double bonds in the ring shifting position. Return of the proton to His 43 is inferred. Ser 17 is hydrogen bonded to His 43 and probably has a role in tuning the pKa of His 43, but this role is not yet explored in the literature.

Catalytic Residues Roles

UniProt PDB* (1f2v)
His43 His43(52)A His 43 acts as a proton donor to the nitrogen of the C ring of the substrate. It probably also deprotonates the product at the same position. hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
*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

proton transfer, overall reactant used, intermediate formation, pericyclic reaction, sigmatropic rearrangement, intermediate terminated, overall product formed, native state of enzyme regenerated

References

  1. Shipman LW et al. (2001), Structure, 9, 587-596. Crystal Structure of Precorrin-8x Methyl Mutase. DOI:10.1016/s0969-2126(01)00618-9. PMID:11470433.
  2. Cuff ME et al. (2005), Proteins, 58, 751-754. Crystal structure of a predicted precorrin-8x methylmutase from Thermoplasma acidophilum. DOI:10.1002/prot.20022. PMID:15609338.

Step 1. The nitrogen of one of the precorrin 8X rings deprotonates His43.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
His43(52)A hydrogen bond donor
His43(52)A proton donor

Chemical Components

proton transfer, overall reactant used, intermediate formation

Step 2. The protonated ring then undergoes a sigmatropic rearrangement.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
His43(52)A hydrogen bond acceptor

Chemical Components

pericyclic reaction, sigmatropic rearrangement, intermediate formation

Step 3. His43 deprotonates the ring, resulting in the hydrogenobyrinate product.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
His43(52)A hydrogen bond acceptor
His43(52)A proton acceptor

Chemical Components

proton transfer, intermediate terminated, overall product formed, native state of enzyme regenerated
Download: Image, Marvin File

Step 1. The nitrogen of one of the precorrin 8X rings deprotonates His43.

Step 2. The protonated ring then undergoes a sigmatropic rearrangement.

Step 3. His43 deprotonates the ring, resulting in the hydrogenobyrinate product.

Products.

Contributors

Gemma L. Holliday, Daniel E. Almonacid, Jonathan T. W. Ng, James Willey