3DHV

Crystal structure of DltA protein in complex with D-alanine adenylate

Summary for 3DHV

• Entry DOI: 10.2210/pdb3dhv/pdb
• Descriptor: D-alanine-poly(phosphoribitol) ligase, D-ALANINE, ADENOSINE MONOPHOSPHATE, ... (4 entities in total)
• Functional Keywords: dlta, amp-forming domain, d-alanine, adenylation, d-alanine carrier protein ligase, cytoplasm, ligase
• Biological source: Bacillus cereus
• Cellular location: Cytoplasm (By similarity): Q81G39
• Total number of polymer chains: 1
• Total formula weight: 58001.91

Authors

Du, L.,He, Y.,Luo, Y. (deposition date: 2008-06-18, release date: 2008-11-04, Last modification date: 2023-08-30)

Primary citation

Du, L.,He, Y.,Luo, Y.
Crystal structure and enantiomer selection by D-alanyl carrier protein ligase DltA from Bacillus cereus.
Biochemistry, 47:11473-11480, 2008

PubMed Abstract: Ubiquitous D-alanylation of lipoteichoic acids modulates the surface charge and ligand binding of the gram-positive cell wall. Disruption of the bacterial DltABCD gene involved in teichoic acid alanylation, as well as inhibition of the DltA protein, has been shown to increase a gram-positive bacterium's susceptibility to antibiotics. The DltA D-alanyl carrier protein ligase promotes a two-step process starting with adenylation of D-alanine. We have determined the 2.0 A resolution crystal structure of a DltA protein from Bacillus cereus in complex with the D-alanine adenylate intermediate of the first reaction. Despite the low level of sequence similarity, the DltA structure resembles known structures of adenylation domains such as the acetyl-CoA synthetase. The enantiomer selection appears to be enhanced by the medium-sized side chain of Cys-269. The Ala-269 mutant protein shows marked loss of such selection. The network of noncovalent interactions between the D-alanine adenylate and DltA provides structure-based rationale for aiding the design of tight-binding DltA inhibitors for combating infectious gram-positive bacteria such as the notorious methicillin-resistant Staphylococcus aureus.

PubMed: 18847223
DOI: 10.1021/bi801363b

Experimental method

X-RAY DIFFRACTION (2 Å)