AASDH (ACSF4-U26) is a β-alanine-activating enzyme that catalyzes an ATP-dependent reaction forming a covalent acyl-enzyme thioester intermediate with β-alanine, with near-absolute substrate specificity for β-alanine among the standard amino acids and a KM of ~5 µM PMID:24467666. Catalysis depends on a phosphopantetheine cofactor: a point mutant lacking the phosphopantetheine attachment site fails to form the thioester bond PMID:24467666. The β-alanine transfer activity resides in the adenylation domain, since deletion of the C-terminal PQQDH-related domain does not abolish transfer onto thiol acceptors; the physiological function of this C-terminal domain has not been characterized in the available corpus PMID:24467666. Beyond this in vitro activation and transfer chemistry, no downstream pathway or in vivo role for AASDH has been established in the available corpus.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2014 | High | Vertebrate AASDH (ACSF4-U26) is a β-alanine-activating enzyme: purified recombinant mouse ACSF4-U26 formed a covalent thioester bond with β-alanine in an ATP-dependent reaction, with a KM of ~5 µM for β-alanine. A point mutant lacking the phosphopantetheine attachment site failed to form this bond, confirming that the phosphopantetheine cofactor is required for catalysis. Competition experiments showed near-absolute specificity for β-alanine among the 20 standard amino acids. | PMID:24467666 | The FEBS journal |
| 2014 | Medium | The PQQDH-related C-terminal domain of AASDH (ACSF4-U26) is not required for β-alanine transfer onto thiol acceptors (cysteine, cysteamine, DTT), indicating that this transfer activity resides in the adenylation domain rather than the C-terminal domain. However, this thiol-transfer activity was judged physiologically irrelevant based on its non-specific nature. | PMID:24467666 | The FEBS journal |