Glycerophosphodiester phosphodiesterase

 

Glycerophosphoryl diester phosphodiesterases display broad specificity for glycerophosphodiesters; glycerophosphocholine, glycerophosphoethanolamine, glycerophosphoglycerol, and bis(glycerophosphoglycerol) all of which are are hydrolysed by this enzyme. Although this enzyme will function with Ca(II) ions, it more active with Mg(II) ions.

 

Reference Protein and Structure

Sequence
Q8RB32 UniProt IPR004129 (Sequence Homologues) (PDB Homologues)
Biological species
Caldanaerobacter subterraneus subsp. tengcongensis MB4 (Bacteria) Uniprot
PDB
2pz0 - Crystal structure of Glycerophosphodiester Phosphodiesterase (GDPD) from T. tengcongensis (1.91 Å) PDBe PDBsum 2pz0
Catalytic CATH Domains
3.20.20.190 CATHdb (see all for 2pz0)
Cofactors
Magnesium(2+) (1), Water (2) Metal MACiE
Click To Show Structure

Enzyme Reaction (EC:3.1.4.46)

water
CHEBI:15377ChEBI
+
sn-glycerophosphodiester(1-)
CHEBI:83408ChEBI
→
alcohol
CHEBI:30879ChEBI
+
sn-glycerol 3-phosphate(2-)
CHEBI:57597ChEBI
+
hydron
CHEBI:15378ChEBI
Alternative enzyme names: IgD-binding protein D, Gene hpd protein, Glycerophosphoryl diester phosphodiesterase,

Enzyme Mechanism

Introduction

His17 deprotonates the substrate alcohol, which initiates a nucleophilic attack on the phosphate group, eliminating the product alcohol with concomitant deprotonation of His59. His59 then deprotonates water, which initiates a nucleophilic attack on the phosphate group, destroying the cyclic intermediate with concomitant deprotonation of His17.

Catalytic Residues Roles

UniProt PDB* (2pz0)
Glu35, Asp37, Glu110 Glu44A, Asp46A, Glu119A Involved in coordinating the magnesium ion. metal ligand
Asp230 Asp239A Increases the basicity of the general acid/base His17. increase basicity, hydrogen bond acceptor, increase acidity
His8, His50 His17A, His59A Acts as a general acid/base. hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
Arg9, Lys112 Arg18A, Lys121A Acts to stabilise the transition states and reactive intermediates formed. hydrogen bond donor, electrostatic stabiliser, steric role
*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

intramolecular elimination, proton transfer, intermediate formation, overall reactant used, overall product formed, intermediate terminated, native state of enzyme regenerated, bimolecular nucleophilic substitution

References

  1. Shi L et al. (2008), Proteins, 72, 280-288. Crystal structure of glycerophosphodiester phosphodiesterase (GDPD) from Thermoanaerobacter tengcongensis , a metal ion-dependent enzyme: Insight into the catalytic mechanism. DOI:10.1002/prot.21921. PMID:18214974.

Step 1. His17 deprotonates the substrate alcohol, which initiates a nucleophilic attack on the phosphate group, eliminating the product alcohol with concomitant deprotonation of His59

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
His17A hydrogen bond acceptor, hydrogen bond donor
Asp239A hydrogen bond acceptor, increase basicity
His59A hydrogen bond donor
Lys121A electrostatic stabiliser, hydrogen bond donor
Arg18A electrostatic stabiliser, steric role, hydrogen bond donor
Glu44A metal ligand
Asp46A metal ligand
Glu119A metal ligand
His59A proton donor
His17A proton acceptor

Chemical Components

ingold: intramolecular elimination, proton transfer, intermediate formation, overall reactant used, overall product formed

Step 2. His59 deprotonates water, which initiates a nucleophilic attack on the phosphate group, destroying the cyclic intermediate with concomitant deprotonation of His17

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
His17A hydrogen bond donor
Asp239A hydrogen bond acceptor, increase acidity
His59A hydrogen bond acceptor
Lys121A electrostatic stabiliser, hydrogen bond donor
Arg18A electrostatic stabiliser, steric role, hydrogen bond donor
Glu44A metal ligand
Asp46A metal ligand
Glu119A metal ligand
His17A proton donor
His59A proton acceptor

Chemical Components

proton transfer, intermediate terminated, overall reactant used, overall product formed, native state of enzyme regenerated, ingold: bimolecular nucleophilic substitution
Download: Image, Marvin File

Step 1. His17 deprotonates the substrate alcohol, which initiates a nucleophilic attack on the phosphate group, eliminating the product alcohol with concomitant deprotonation of His59

Step 2. His59 deprotonates water, which initiates a nucleophilic attack on the phosphate group, destroying the cyclic intermediate with concomitant deprotonation of His17

Products.

Contributors

Gemma L. Holliday, James Willey