AOAH Recombinant Rabbit mAb (S-3713-10)

Acyloxyacyl hydrolase (AOAH) is a specific lipase predominantly encoded by the AOAH gene on chromosome 7, highly expressed in phagocytes such as macrophages and neutrophils, and stored within endocytic and cytoplasmic vesicles. Its most distinctive structural feature is that it is the only mammalian enzyme—apart from acid sphingomyelinase—that contains a GDSL hydrolase catalytic domain fused to a saposin-like B-type domain. The crystal structure published in 2021 (PDB: 5W7A) further revealed that this enzyme anchors its substrate via a hydrophobic platform formed by the saposin domain, while a narrow hydrophobic tunnel within the catalytic domain precisely inserts into and cleaves the secondary acyloxyacyl chains of lipid A, thereby converting intact hexa-acylated lipopolysaccharide (LPS) into an immunologically inert molecule bearing only four primary acyl chains. Contrary to classical assumptions, AOAH is not a broad-spectrum lipase; its catalytic efficiency is tightly regulated by the presentation form of LPS in the extracellular environment. When LPS forms a soluble monomeric complex with CD14, its secondary acyl chains become fully exposed, and AOAH's catalytic efficiency is up to 100-fold higher than when acting on LPS aggregates. However, once the substrate is transferred to MD-2 and loaded onto TLR4, the acyl chains are sequestered, rendering the complex resistant to AOAH. This dynamic regulatory mechanism ensures that negative feedback occurs only after TLR4 signaling has been activated. Functionally, the core physiological significance of AOAH lies in its ability to actively terminate endotoxin tolerance. AOAH-knockout mice remain hyporesponsive to restimulation for up to 21 days following a single LPS challenge (with significantly reduced TNF-α and IL-6 secretion), and their peritoneal macrophages retain immunologically active, non-deacylated LPS. These mice also exhibit significantly increased mortality upon sublethal E. coli infection due to impaired bacterial clearance. Furthermore, genetic polymorphisms in this gene are significantly associated with asthma, IgE levels, hypertension, and HIV-1 susceptibility. AOAH has also been shown to possess oxidized phospholipid hydrolase activity, alleviating acute lung injury by clearing pro-inflammatory oxidized phospholipid molecules. In summary, AOAH is not only an indispensable enzyme for the active "awakening" of the host from the immune paralysis following Gram-negative bacterial infection, but the ongoing elucidation of its substrate spectrum and tissue-specific expression regulatory mechanisms is positioning it as a potential interventional target for treating inflammatory diseases such as endotoxemia, inflammatory bowel disease, and asthma.