8sw0

Puromycin sensitive aminopeptidasePuromycin sensitive aminopeptidase

Structural highlights

8sw0 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.301Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PSA_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 PubMed

Puromycin-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

↑ Yamamoto Y, Li YH, Ushiyama I, Nishimura A, Ohkubo I, Nishi K. Puromycin-sensitive alanyl aminopeptidase from human liver cytosol: purification and characterization. Forensic Sci Int. 2000 Sep 11;113(1-3):143-6. PMID:10978616 doi:10.1016/s0379-0738(00)00280-2
↑ Stoltze L, Schirle M, Schwarz G, Schröter C, Thompson MW, Hersh LB, Kalbacher H, Stevanovic S, Rammensee HG, Schild H. Two new proteases in the MHC class I processing pathway. Nat Immunol. 2000 Nov;1(5):413-8. PMID:11062501 doi:10.1038/80852
↑ Sengupta S, Horowitz PM, Karsten SL, Jackson GR, Geschwind DH, Fu Y, Berry RW, Binder LI. Degradation of tau protein by puromycin-sensitive aminopeptidase in vitro. Biochemistry. 2006 Dec 19;45(50):15111-9. PMID:17154549 doi:10.1021/bi061830d
↑ Bhutani N, Venkatraman P, Goldberg AL. Puromycin-sensitive aminopeptidase is the major peptidase responsible for digesting polyglutamine sequences released by proteasomes during protein degradation. EMBO J. 2007 Mar 7;26(5):1385-96. PMID:17318184 doi:10.1038/sj.emboj.7601592
↑ Kim E, Kwak H, Ahn K. Cytosolic aminopeptidases influence MHC class I-mediated antigen presentation in an allele-dependent manner. J Immunol. 2009 Dec 1;183(11):7379-87. PMID:19917696 doi:10.4049/jimmunol.0901489
↑ Madabushi S, Chow KM, Song ES, Goswami A, Hersh LB, Rodgers DW. Structure of puromycin-sensitive aminopeptidase and polyglutamine binding. PLoS One. 2023 Jul 13;18(7):e0287086. PMID:37440518 doi:10.1371/journal.pone.0287086

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OCA

[1] Yamamoto Y, Li YH, Ushiyama I, Nishimura A, Ohkubo I, Nishi K. Puromycin-sensitive alanyl aminopeptidase from human liver cytosol: purification and characterization. Forensic Sci Int. 2000 Sep 11;113(1-3):143-6. PMID:10978616 doi:10.1016/s0379-0738(00)00280-2

[2] Stoltze L, Schirle M, Schwarz G, Schröter C, Thompson MW, Hersh LB, Kalbacher H, Stevanovic S, Rammensee HG, Schild H. Two new proteases in the MHC class I processing pathway. Nat Immunol. 2000 Nov;1(5):413-8. PMID:11062501 doi:10.1038/80852

[3] Sengupta S, Horowitz PM, Karsten SL, Jackson GR, Geschwind DH, Fu Y, Berry RW, Binder LI. Degradation of tau protein by puromycin-sensitive aminopeptidase in vitro. Biochemistry. 2006 Dec 19;45(50):15111-9. PMID:17154549 doi:10.1021/bi061830d

[4] Bhutani N, Venkatraman P, Goldberg AL. Puromycin-sensitive aminopeptidase is the major peptidase responsible for digesting polyglutamine sequences released by proteasomes during protein degradation. EMBO J. 2007 Mar 7;26(5):1385-96. PMID:17318184 doi:10.1038/sj.emboj.7601592

[5] Kim E, Kwak H, Ahn K. Cytosolic aminopeptidases influence MHC class I-mediated antigen presentation in an allele-dependent manner. J Immunol. 2009 Dec 1;183(11):7379-87. PMID:19917696 doi:10.4049/jimmunol.0901489

[6] Madabushi S, Chow KM, Song ES, Goswami A, Hersh LB, Rodgers DW. Structure of puromycin-sensitive aminopeptidase and polyglutamine binding. PLoS One. 2023 Jul 13;18(7):e0287086. PMID:37440518 doi:10.1371/journal.pone.0287086

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