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From Proteopedia
Puromycin sensitive aminopeptidase
Structural highlights
FunctionPSA_HUMAN Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins. Digests tau from normal brain more efficiently than tau from Alzheimer disease brain.[1] [2] [3] [4] [5] Publication Abstract from PubMedPuromycin-sensitive aminopeptidase (E.C. 3.4.11.14, UniProt P55786), a zinc metallopeptidase belonging to the M1 family, degrades a number of bioactive peptides as well as peptides released from the proteasome, including polyglutamine. We report the crystal structure of PSA at 2.3 A. Overall, the enzyme adopts a V-shaped architecture with four domains characteristic of the M1 family aminopeptidases, but it is in a less compact conformation compared to most M1 enzymes of known structure. A microtubule binding sequence is present in a C-terminal HEAT repeat domain of the enzyme in a position where it might serve to mediate interaction with tubulin. In the catalytic metallopeptidase domain, an elongated active site groove lined with aromatic and hydrophobic residues and a large S1 subsite may play a role in broad substrate recognition. The structure with bound polyglutamine shows a possible interacting mode of this peptide, which is supported by mutation. Structure of puromycin-sensitive aminopeptidase and polyglutamine binding.,Madabushi S, Chow KM, Song ES, Goswami A, Hersh LB, Rodgers DW PLoS One. 2023 Jul 13;18(7):e0287086. doi: 10.1371/journal.pone.0287086. , eCollection 2023. PMID:37440518[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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