3-hexulose-6-phosphate isomerase

 

3-hexulose-6-phosphate (PHI) catalyses the isomerisation between 3-hexulose 6-phosphate and fructose 6-phosphate. PHI is part of the ribulose monophosphate (RuMP) pathway, which in one direction removes the toxic metabolite formaldehyde by assimilation into fructose-6-phosphate [PMID:10648518]. In the other direction, in species lacking a complete pentose phosphate pathway, the RuMP pathway yields ribulose-5-phosphate, necessary for nucleotide biosynthesis, at the cost of also yielding formaldehyde. These latter species tend usually have a formaldehyde-activating enzyme to attach formaldehyde to the C1 carrier tetrahydromethanopterin.

 

Reference Protein and Structure

Sequence
P42404 UniProt (5.3.1.27) IPR017552 (Sequence Homologues) (PDB Homologues)
Biological species
Bacillus subtilis subsp. subtilis str. 168 (Bacteria) Uniprot
PDB
1m3s - Crystal structure of YckF from Bacillus subtilis (1.95 Å) PDBe PDBsum 1m3s
Catalytic CATH Domains
3.40.50.10490 CATHdb (see all for 1m3s)
Click To Show Structure

Enzyme Reaction (EC:5.3.1.27)

D-arabino-hex-3-ulose 6-phosphate(2-)
CHEBI:58542ChEBI
→
beta-D-fructofuranose 6-phosphate(2-)
CHEBI:57634ChEBI
Alternative enzyme names: 3-hexulose-6-phosphate isomerase, Phospho-3-hexuloisomerase, PHI, 6-phospho-3-hexulose isomerase, YckF,

Enzyme Mechanism

Introduction

The phosphate-binding site is constructed by strictly conserved and characteristic loops between alpha helices and beta strands, employing several hydroxyl groups from serine and threonine residues and a number of backbone nitrogens. From several potentially catalytic residues, Glu-152 has been identified as the most probable catalytic nucleophile. There is no full mechanism proposal for this enzyme at the moment.

Catalytic Residues Roles

UniProt PDB* (1m3s)
Glu152 Glu152(153)B Proposed as the most likely residue to be the catalytic nucleophile. covalent catalysis
His60, Asp160, Ser149 His60(61)A, Asp160(161)A, Ser149(150)B Stabilises arginine electrostatic stabiliser
Ser88 Ser88(89)B Phosphate binding and stabilising electrostatic stabiliser
Arg57, Arg46 Arg57(58)A, Arg46(47)B Activates Glu152 enhance reactivity
*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. Sanishvili R et al. (2004), J Struct Biol, 148, 98-109. Crystal structure of Bacillus subtilis YckF: structural and functional evolution. DOI:10.1016/j.jsb.2004.04.006. PMID:15363790.
  2. Martinez-Cruz LA et al. (2002), Structure, 10, 195-204. Crystal structure of MJ1247 protein from M. jannaschii at 2.0 A resolution infers a molecular function of 3-hexulose-6-phosphate isomerase. PMID:11839305.
  3. Mitsui R et al. (2000), J Bacteriol, 182, 944-948. A novel operon encoding formaldehyde fixation: the ribulose monophosphate pathway in the gram-positive facultative methylotrophic bacterium Mycobacterium gastri MB19. PMID:10648518.

Step 1.

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Catalytic Residues Roles

Residue Roles
Glu152(153)B covalent catalysis
Arg46(47)B enhance reactivity
Arg57(58)A enhance reactivity
His60(61)A electrostatic stabiliser
Ser88(89)B electrostatic stabiliser
Ser149(150)B electrostatic stabiliser
Asp160(161)A electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Gemma L. Holliday