8FFF
Crystal structure of Staphylococcus aureus D-alanine D-alanine ligase enzyme in complex with acetate
Summary for 8FFF
| Entry DOI | 10.2210/pdb8fff/pdb |
| Descriptor | D-alanine--D-alanine ligase, ACETATE ION (3 entities in total) |
| Functional Keywords | d-alanine d-alanie, s.aureus, cell wall biosynthesis, omega loop, ligase |
| Biological source | Staphylococcus aureus |
| Total number of polymer chains | 1 |
| Total formula weight | 40161.23 |
| Authors | Jayasinghe, Y.P.,Ronning, D.R. (deposition date: 2022-12-08, release date: 2024-05-08, Last modification date: 2024-05-15) |
| Primary citation | Panda, S.,Jayasinghe, Y.P.,Shinde, D.D.,Bueno, E.,Stastny, A.,Bertrand, B.P.,Chaudhari, S.S.,Kielian, T.,Cava, F.,Ronning, D.R.,Thomas, V.C. Staphylococcus aureus counters organic acid anion-mediated inhibition of peptidoglycan cross-linking through robust alanine racemase activity. Biorxiv, 2024 Cited by PubMed Abstract: Weak organic acids are commonly found in host niches colonized by bacteria, and they can inhibit bacterial growth as the environment becomes acidic. This inhibition is often attributed to the toxicity resulting from the accumulation of high concentrations of organic anions in the cytosol, which disrupts cellular homeostasis. However, the precise cellular targets that organic anions poison and the mechanisms used to counter organic anion intoxication in bacteria have not been elucidated. Here, we utilize acetic acid, a weak organic acid abundantly found in the gut to investigate its impact on the growth of . We demonstrate that acetate anions bind to and inhibit d-alanyl-d-alanine ligase (Ddl) activity in . Ddl inhibition reduces intracellular d-alanyl-d-alanine (d-Ala-d-Ala) levels, compromising staphylococcal peptidoglycan cross-linking and cell wall integrity. To overcome the effects of acetate-mediated Ddl inhibition, maintains a high intracellular d-Ala pool through alanine racemase (Alr1) activity and additionally limits the flux of d-Ala to d-glutamate by controlling d-alanine aminotransferase (Dat) activity. Surprisingly, the of acetate intoxication in is common to multiple biologically relevant weak organic acids indicating that Ddl is a conserved target of small organic anions. These findings suggest that may have evolved to maintain high intracellular d-Ala concentrations, partly to counter organic anion intoxication. PubMed: 38293037DOI: 10.1101/2024.01.15.575639 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.92 Å) |
Structure validation
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