Acetate kinase

Acetate_kinase
Acetate kinase homodimer, Methanosarcina thermophila[1]
Identifiers
SymbolAcetate_kinase
PfamPF00871
Pfam clanCL0108
InterProIPR000890
PROSITEPDOC00826
SCOP21g99 / SCOPe / SUPFAM
Available protein structures:
PDB  IPR000890 PF00871 (ECOD; PDBsum)  
AlphaFold

In molecular biology, acetate kinase (EC 2.7.2.1), which is predominantly found in micro-organisms, facilitates the production of acetyl-CoA by phosphorylating acetate in the presence of ATP and a divalent cation.[2]

Function

The enzyme characterised from many species of bacteria and archaea including Bacillus subtilis,[3] Lactobacillus sanfranciscensis,[4] and Methanosarcina thermophila[5] catalyses the phosphorylation of acetic acid:

ATP +
 
2D representation of the chemical structure of acetic acid .
acetic acid
 
 
 
Reversible left-right reaction arrow
 
 
 
ADP +
 
2D representation of the chemical structure of acetyl phosphate.
acetyl phosphate

A phosphate group is transferred from the cofactor, adenosine triphosphate (ATP), which is converted to adenosine diphosphate (ADP).

The enzyme is not always specific for acetate: in Methanosarcina thermophila it also acts on propionic acid.[6] In one variant found in Escherichia coli this is the major function of the enzyme, when it degrades L-threonine.[7]

Role in metabolism

Short-chain fatty acids (SCFAs) play a major role in carbon cycle and can be utilized as a source of carbon and energy by bacteria. Salmonella typhimurium propionate kinase (StTdcD) catalyzes reversible transfer of the γ-phosphate of ATP to propionate during l-threonine degradation to propionate. Kinetic analysis revealed that StTdcD possesses broad ligand specificity and could be activated by various SCFAs (propionate>acetate≈butyrate), nucleotides (ATP≈GTP>CTP≈TTP; dATP>dGTP>dCTP) and metal ions (Mg2+≈Mn2+>Co2+). Inhibition of StTdcD by tricarboxylic acid (TCA) cycle intermediates such as citrate, succinate, α-ketoglutarate and malate suggests that the enzyme could be under plausible feedback regulation. Crystal structures of StTdcD bound to PO4 (phosphate), AMP, ATP, Ap4 (adenosine tetraphosphate), GMP, GDP, GTP, CMP and CTP revealed that binding of nucleotide mainly involves hydrophobic interactions with the base moiety and could account for the broad biochemical specificity observed between the enzyme and nucleotides. Modelling and site-directed mutagenesis studies suggest Ala88 to be an important residue involved in determining the rate of catalysis with SCFA substrates. Molecular dynamics simulations on monomeric and dimeric forms of StTdcD revealed plausible open and closed states, and also suggested role for dimerization in stabilizing segment 235-290 involved in interfacial interactions and ligand binding. Observation of an ethylene glycol molecule bound sufficiently close to the γ-phosphate in StTdcD complexes with triphosphate nucleotides supports direct in-line phosphoryl transfer.[3][8] The enzyme is important in the process of glycolysis, enzyme levels being increased in the presence of excess glucose. The growth of a bacterial mutant lacking acetate kinase has been shown to be inhibited by glucose, suggesting that the enzyme is involved in excretion of excess carbohydrate.[3] A related enzyme, butyrate kinase, facilitates the formation of butyryl-CoA by phosphorylating butyrate in the presence of ATP to form butyryl phosphate.[8]

References

  1. ↑ Buss, Kathryn A.; Cooper, David R.; Ingram-Smith, Cheryl; Ferry, James G.; Sanders, David Avram; Hasson, Miriam S. (2001). "Urkinase: Structure of Acetate Kinase, a Member of the ASKHA Superfamily of Phosphotransferases". Journal of Bacteriology. 183 (2): 680–686. doi:10.1128/JB.183.2.680-686.2001. PMC 94925. PMID 11133963.
  2. ↑ Enzyme 2.7.2.1 at KEGG Pathway Database.
  3. 1 2 3 Grundy FJ, Waters DA, Allen SH, Henkin TM (November 1993). "Regulation of the Bacillus subtilis acetate kinase gene by CcpA". J. Bacteriol. 175 (22): 7348–55. doi:10.1128/jb.175.22.7348-7355.1993. PMC 206879. PMID 8226682.
  4. ↑ Knorr, Ruth; Ehrmann, Matthias A.; Vogel, Rudi F. (2001). "Cloning, expression, and characterization of acetate kinase from Lactobacillus sanfranciscensis". Microbiological Research. 156 (3): 267–277. doi:10.1078/0944-5013-00114. PMID 11716215.
  5. ↑ Gorrell, Andrea; Lawrence, Sarah H.; Ferry, James G. (2005). "Structural and Kinetic Analyses of Arginine Residues in the Active Site of the Acetate Kinase from Methanosarcina thermophila". Journal of Biological Chemistry. 280 (11): 10731–10742. doi:10.1074/jbc.M412118200. PMID 15647264.
  6. ↑ Ingram-Smith, Cheryl; Gorrell, Andrea; Lawrence, Sarah H.; Iyer, Prabha; Smith, Kerry; Ferry, James G. (2005). "Characterization of the Acetate Binding Pocket in the Methanosarcina thermophila Acetate Kinase". Journal of Bacteriology. 187 (7): 2386–2394. doi:10.1128/JB.187.7.2386-2394.2005. PMC 1065240. PMID 15774882.
  7. ↑ Heßlinger, Christian; Fairhurst, Shirley A.; Sawers, Gary (1998). "Novel keto acid formate-lyase and propionate kinase enzymes are components of an anaerobic pathway in Escherichia coli that degrades L-threonine to propionate". Molecular Microbiology. 27 (2): 477–492. doi:10.1046/j.1365-2958.1998.00696.x. PMID 9484901.
  8. 1 2 Oultram JD, Burr ID, Elmore MJ, Minton NP (September 1993). "Cloning and sequence analysis of the genes encoding phosphotransbutyrylase and butyrate kinase from Clostridium acetobutylicum NCIMB 8052". Gene. 131 (1): 107–12. doi:10.1016/0378-1119(93)90677-U. PMID 8396545.
This article incorporates text from the public domain Pfam and InterPro: IPR000890
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