Shigella flexneri, a Gram-negative bacterium that damages th...
| created | [InstanceEdit:9956599] Shamovsky, Veronica, 2025-06-13 |
| dbId | 9956645 |
| displayName | Shigella flexneri, a Gram-negative bacterium that damages th... |
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| modified | [InstanceEdit:9963583] Shamovsky, Veronica, 2025-08-14 |
| schemaClass | Summation |
| text | Shigella flexneri, a Gram-negative bacterium that damages the colonic epithelium and causes bacillary dysentery in humans, secretes the effector OspC3 via the type III secretion system. OspC3 inhibits caspase-4 (CASP4) and suppresses CASP4-mediated pyroptosis, a lytic form of cell death triggered by intracellular lipopolysaccharide (LPS) (Kobayashi T. et al., 2013; Li Z. et al., 2021; Hou Y. et al., 2023). Structural and biochemical analyses have shown that OspC3 recognizes CASP4 via its ankyrin repeat domain (Kobayashi T. et al., 2013; Li Z. et al., 2021; Hou Y. et al., 2023). OspC3 can bind both procaspase (p30) and processed (p20:p10; not depicted in this Reactome event) forms of CASP4 (Li Z. et al., 2021). It catalyzes ADP-riboxanation of CASP4 at arginine 314 (R314) by transferring ADP-ribose from NAD? to the N? atom of the arginine side chain, followed by deamination of an N? group to generate an oxazolidine ring structure (Li Z. et al., 2021; Hou Y. et al., 2023). The catalytic activity of OspC3 is enhanced by calcium-free calmodulin (CALM), which binds OspC3 and reconfigures its catalytic pocket to permit NAD? binding. CALM binding also promotes the formation of a stable ternary complex between CALM:OspC3 and CASP4 (Li Z. et al., 2021; Hou Y. et al., 2023). |
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