D-alanine—D-alanine ligase

D-alanine—D-alanine ligase (also known as D-Ala-D-Ala ligase or Ddl) is an enzyme that plays a crucial role in the bacterial cell wall synthesis. It is involved in the last step of the cytoplasmic phase of peptidoglycan biosynthesis.

Function

D-alanine—D-alanine ligase catalyzes the ATP-dependent ligation of two D-alanine molecules to form D-alanyl-D-alanine, a critical component of the peptidoglycan layer of the bacterial cell wall. This reaction involves the formation of a phosphorylated intermediate and the release of inorganic phosphate.

Structure

The enzyme is a monomer with a molecular weight of approximately 37 kDa. It consists of three domains: the N-terminal domain, the C-terminal domain, and the central domain. The active site is located in a cleft between the N-terminal and central domains.

Clinical significance

D-alanine—D-alanine ligase is a target for several antibiotics, including vancomycin and cycloserine. These antibiotics inhibit the enzyme's activity, preventing the formation of the D-alanyl-D-alanine dipeptide and thus disrupting the synthesis of the bacterial cell wall.

See also

• Peptidoglycan
• Vancomycin
• Cycloserine

References

• D-alanine—D-alanine ligase
  D-alanine—D-alanine ligase