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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.

December 2004 / Patterns and text revised.

PROSITE methods (with tools and information) covered by this documentation:

DALA_DALA_LIGASE_1, PS00843; D-alanine--D-alanine ligase signature 1  (PATTERN)

Consensus pattern: H-[GN]-x(2)-[GC]-E-[DNT]-G-x-[LIVMAFT]-[QSAPH]-[GSA] Sequences known to belong to this class detected by the pattern: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00843 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00843 • Scan Swiss-Prot/TrEMBL entries against PS00843 • view ligand binding statistics

Matching PDB structures: 1E4E 1EHI 1IOV 1IOW ... [ALL]

DALA_DALA_LIGASE_2, PS00844; D-alanine--D-alanine ligase signature 2  (PATTERN)

Consensus pattern: [LIVAMSFT]-x(3)-[GAHDVSI]-x-[GSAIVCT]-R-[LIVMCAFST]-[DE]-[LIVMFAYGT]-[LIVMFAR]-x(7,12)-[LIVWCAF]-x-[EK]-[LIVAPMT]-N-[STPA]-x-P-[GA] Sequences known to belong to this class detected by the pattern: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00844 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00844 • Scan Swiss-Prot/TrEMBL entries against PS00844 • view ligand binding statistics

Matching PDB structures: 1E4E 1EHI 1IOV 1IOW ... [ALL]

1	Authors	Zawadzke L.E., Bugg T.D., Walsh C.T.
	Title	Existence of two D-alanine:D-alanine ligases in Escherichia coli: cloning and sequencing of the ddlA gene and purification and characterization of the DdlA and DdlB enzymes.
	Source	Biochemistry 30:1673-1682(1991).
	PubMed ID	1993184

2	Authors	Dutka-Malen S., Molinas C., Arthur M., Courvalin P.
	Source	Gene 112:53-58(1992).

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