CDP-diacylglycerol diphosphatase

 

5-aminoimidazole ribotide (AIR) is a branch point metabolite in the biosynthetic pathways of purines and thiamin. Although AIR cannot be efficiently taken up by most bacteria, 5-aminoimidazole riboside (AIRs) can. Aminoimidazole riboside kinase catalyses the phosphorylation of AIRs into AIR to feed into purine and thiamin biosynthesis pathways.

 

Reference Protein and Structure

Sequence
Q8ZKR2 UniProt (2.7.1.4, 3.6.1.26) IPR002139 (Sequence Homologues) (PDB Homologues)
Biological species
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 (Bacteria) Uniprot
PDB
1tz3 - crystal structure of aminoimidazole riboside kinase complexed with aminoimidazole riboside (2.9 Å) PDBe PDBsum 1tz3
Catalytic CATH Domains
3.40.1190.20 CATHdb (see all for 1tz3)
Click To Show Structure

Enzyme Reaction (EC:3.6.1.26)

water
CHEBI:15377ChEBI
+
CDP-diacylglycerol(2-)
CHEBI:58332ChEBI
→
1,2-diacyl-sn-glycerol 3-phosphate(2-)
CHEBI:58608ChEBI
+
cytidine 5'-monophosphate(2-)
CHEBI:60377ChEBI
+
hydron
CHEBI:15378ChEBI
Alternative enzyme names: CDP diacylglycerol hydrolase, Cytidine diphosphodiacylglycerol pyrophosphatase, CDP-diacylglycerol pyrophosphatase, CDP-diacylglycerol phosphatidylhydrolase,

Enzyme Mechanism

Introduction

The mechanism proposed is mainly by homology to other ribokinases, such as human adenosine kinase. Asp 252 is a general base and deprotonates the 5' hydroxyl group of the ribose. The deprotonated hydroxyl attacks the gamma-phosphate of ATP in an inline displacement mechanism. The backbone amides of Gly 249, Ala 250, Gly 251 and Asp 252 act as an anion hole to stabilise negative charge build-up in the pentacovalent transition state. The products are AIR and ADP.

Catalytic Residues Roles

UniProt PDB* (1tz3)
Asp252 Asp252(272)A The side chain of Asp 252 deprotonates the 5' hydroxyl of the substrate, making it more nucleophilic.
The main chain amide acts as an anion hole to stabilise charge build-up in the transition state.		 proton shuttle (general acid/base), electrostatic stabiliser
Gly249 (main-N) Gly249(269)A (main-N) The main chain amide of Gly 249 acts as an anion hole to stabilise charge build-up in the transition state. electrostatic stabiliser
Ala250 (main-N) Ala250(270)A (main-N) The main chain amide of Ala 250 acts as an anion hole to stabilise charge build-up in the transition state. electrostatic stabiliser
Gly251 (main-N) Gly251(271)A (main-N) The main chain amide of Gly 251 acts as an anion hole to stabilise charge build-up in the transition state. 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. Zhang Y et al. (2004), Structure, 12, 1809-1821. Crystal Structure of an Aminoimidazole Riboside Kinase from Salmonella enterica. DOI:10.1016/j.str.2004.07.020. PMID:15458630.

Step 1.

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Catalytic Residues Roles

Residue Roles
Gly249(269)A (main-N) electrostatic stabiliser
Gly251(271)A (main-N) electrostatic stabiliser
Asp252(272)A proton shuttle (general acid/base), electrostatic stabiliser
Ala250(270)A (main-N) electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Jonathan T. W. Ng, Gemma L. Holliday, Charity Hornby