D-alanine--D-alanine ligase signatures

D-alanine--D-alanine ligase (EC 6.3.2.4) is a bacterial enzyme involved in cell-wall biosynthesis. It participates in forming UDP-N-acetylmuramyl pentapeptide, the peptidoglycan precursor.

In Escherichia coli and related bacteria, there are two different D-ala--D-ala ligase isozymes (genes ddlA and ddlB) [1]. In Enterobacterium faecium and gallinarum, genes vanA and vanC encode D-ala--D-ala ligases of altered specificity, which catalyze ester bond formations between D-ala and various D-hydroxy acids [2]. They are required for resistance to glycopeptide antibiotics, such as vancomycin which inhibits late stages in cell-wall synthesis.

These enzymes are proteins of 300 to 360 amino acids. There are many conserved regions, of which we selected two as signature patterns. The first pattern, which is Gly-rich and could be involved in ATP-binding, is located near the N-terminal extremity, the second is in the C-terminal section.