7vhv
From Proteopedia
Crystal structure of S. aureus D-alanine alanyl carrier protein ligase
Structural highlights
FunctionDLTA_STAAM Catalyzes the first step in the D-alanylation of lipoteichoic acid (LTA), the activation of D-alanine and its transfer onto the D-alanyl carrier protein (Dcp) DltC. In an ATP-dependent two-step reaction, forms a high energy D-alanyl-AMP intermediate, followed by transfer of the D-alanyl residue as a thiol ester to the phosphopantheinyl prosthetic group of the Dcp. D-alanylation of LTA plays an important role in modulating the properties of the cell wall in Gram-positive bacteria, influencing the net charge of the cell wall. Publication Abstract from PubMedD-Alanylation of the teichoic acids of the Gram-positive bacterial cell wall plays crucial roles in bacterial physiology and virulence. Deprivation of D-alanine from the teichoic acids of Staphylococcus aureus impairs biofilm and colony formation, induces autolysis and ultimately renders methicillin-resistant S. aureus highly susceptible to antimicrobial agents and host defense peptides. Hence, the D-alanylation pathway has emerged as a promising antibacterial target against drug-resistant S. aureus. D-Alanylation of teichoic acids is mediated via the action of four proteins encoded by the dlt operon, DltABCD, all four of which are essential for the process. In order to develop novel antimicrobial agents against S. aureus, the D-alanyl carrier protein ligase DltA, which is the first protein in the D-alanylation pathway, was focused on. Here, the crystal structure of DltA from the methicillin-resistant S. aureus strain Mu50 is presented, which reveals the unique molecular details of the catalytic center and the role of the P-loop. Kinetic analysis shows that the enantioselectivity of S. aureus DltA is much higher than that of DltA from other species. In the presence of DltC, the enzymatic activity of DltA is increased by an order of magnitude, suggesting a new exploitable binding pocket. This discovery may pave the way for a new generation of treatments for drug-resistant S. aureus. Structural and functional analysis of the D-alanyl carrier protein ligase DltA from Staphylococcus aureus Mu50.,Lee IG, Song C, Yang S, Jeon H, Park J, Yoon HJ, Im H, Kang SM, Eun HJ, Lee BJ Acta Crystallogr D Struct Biol. 2022 Apr 1;78(Pt 4):424-434. doi:, 10.1107/S2059798322000547. Epub 2022 Mar 16. PMID:35362466[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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