Glycerol-3-phosphate O-acyltransferase

 

Glycerol-3-phosphate (1)-acyltransferase (G3PAT) catalyses the attachment of an acyl group from either acyl-carrier proteins (acyl-ACPs) or acyl-CoAs onto the C1 hydroxyl group of glycerol-3-phosphate to give 1-acylglycerol-3-phosphate. Different G3PAT enzymes have different substrate specificities, with some preferring to add the unsaturated fatty acid oleate and others using both oleate and the saturated fatty acid palmitate. The different substrate specificities within this family has been implicated in the sensitivity of plants to chilling temperatures.

 

Reference Protein and Structure

Sequence
P10349 UniProt (2.3.1.15, 2.3.1.n5) IPR016222 (Sequence Homologues) (PDB Homologues)
Biological species
Cucurbita moschata (Crookneck pumpkin) Uniprot
PDB
1k30 - Crystal Structure Analysis of Squash (Cucurbita moschata) glycerol-3-phosphate (1)-acyltransferase (1.9 Å) PDBe PDBsum 1k30
Catalytic CATH Domains
3.40.1130.10 CATHdb (see all for 1k30)
Click To Show Structure

Enzyme Reaction (EC:2.3.1.15)

sn-glycerol 3-phosphate(2-)
CHEBI:57597ChEBI
+
acyl-CoA(4-)
CHEBI:58342ChEBI
→
1-acyl-sn-glycerol 3-phosphate(2-)
CHEBI:57970ChEBI
+
coenzyme A(4-)
CHEBI:57287ChEBI
Alternative enzyme names: 3-glycerophosphate acyltransferase, Alpha-glycerophosphate acyltransferase, sn-glycerol 3-phosphate acyltransferase, sn-glycerol-3-phosphate acyltransferase, ACP:sn-glycerol-3-phosphate acyltransferase, Glycerol 3-phosphate acyltransferase, Glycerol phosphate acyltransferase, Glycerol phosphate transacylase, Glycerophosphate acyltransferase, Glycerophosphate transacylase, Glycerol-3-phosphate O-acyltransferase,

Enzyme Mechanism

Introduction

Glycerol-3-phosphate (1)-acyltransferase is thought to employ a His-Asp dyad resembling that of serine proteases. His 139 acts to deprotonate the C1 hydroxyl group of glycerol-3-phosphate, allowing nucleophilic attack by this group on the carbonyl of acyl-ACP or acyl-CoA. Asp 144 serves to modify the pKa of His 139, allowing it to act as a catalytic base.

Catalytic Residues Roles

UniProt PDB* (1k30)
His167 His139A Proposed to deprotonate the C1 hydroxyl group of glycerol 3-phosphate, allowing this group to attack the fatty acyl substrate. proton acceptor, proton donor
Asp172 Asp144A Proposed to modify the pKa of His 139, allowing it to act as a catalytic base. 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

proton transfer, overall reactant used, bimolecular nucleophilic addition, unimolecular elimination by the conjugate base, overall product formed, cofactor used, inferred reaction step, native state of enzyme regenerated

References

  1. Turnbull AP et al. (2001), Structure, 9, 347-353. Analysis of the Structure, Substrate Specificity, and Mechanism of Squash Glycerol-3-Phosphate (1)-Acyltransferase. DOI:10.1016/s0969-2126(01)00595-0. PMID:11377195.
  2. Heath RJ et al. (1998), J Bacteriol, 180, 1425-1430. A conserved histidine is essential for glycerolipid acyltransferase catalysis. PMID:9515909.

Step 1. His139 deprotonates the hydroxyl group of C1 of glycerol-3-phosphate

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Asp144A electrostatic stabiliser
His139A proton acceptor

Chemical Components

proton transfer, overall reactant used

Step 2. The C1 hydroxyl of glycerol-3-phosphate acts as a nucleophile to attack the carbonyl acyl-CoA.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles

Chemical Components

ingold: bimolecular nucleophilic addition, ingold: unimolecular elimination by the conjugate base, overall product formed, cofactor used

Step 3. In an inferred step CoA is protonated and His139 is deprotonated to regenerate the native state of the enzyme.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
His139A proton donor

Chemical Components

proton transfer, inferred reaction step, native state of enzyme regenerated, overall product formed
Download: Image, Marvin File

Step 1. His139 deprotonates the hydroxyl group of C1 of glycerol-3-phosphate

Step 2. The C1 hydroxyl of glycerol-3-phosphate acts as a nucleophile to attack the carbonyl acyl-CoA.

Step 3. In an inferred step CoA is protonated and His139 is deprotonated to regenerate the native state of the enzyme.

Products.

Contributors

Steven Smith, Gemma L. Holliday, Amelia Brasnett