3dhv
Crystal structure of DltA protein in complex with D-alanine adenylate
Structural highlights
FunctionDLTA_BACCR Involved in the biosynthesis of D-alanyl-lipoteichoic acid (LTA). Catalyzes an ATP-dependent two-step reaction where it forms a high energy D-alanyl AMP intermediate and transfers the alanyl residues from AMP to Dcp (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedUbiquitous 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. Crystal structure and enantiomer selection by D-alanyl carrier protein ligase DltA from Bacillus cereus.,Du L, He Y, Luo Y Biochemistry. 2008 Nov 4;47(44):11473-80. Epub 2008 Oct 11. PMID:18847223[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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