8sw0

From Proteopedia

(Difference between revisions)

Current revision

Puromycin 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8sw0"

Categories: Homo sapiens | Large Structures | Rodgers DW | Sampath S

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8sw0 is ON HOLD  until Paper Publication
+==Puromycin sensitive aminopeptidase==
+<StructureSection load='8sw0' size='340' side='right'caption='[[8sw0]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8sw0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SW0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SW0 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.301&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8sw0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sw0 OCA], [https://pdbe.org/8sw0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sw0 RCSB], [https://www.ebi.ac.uk/pdbsum/8sw0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sw0 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PSA_HUMAN 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.<ref>PMID:10978616</ref> <ref>PMID:11062501</ref> <ref>PMID:17154549</ref> <ref>PMID:17318184</ref> <ref>PMID:19917696</ref>
+<div style="background-color:#fffaf0;">
+== 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.
-Authors:
+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<ref>PMID:37440518</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8sw0" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Rodgers DW]]
+[[Category: Sampath S]]

8sw0

From Proteopedia

Current revision

Puromycin sensitive aminopeptidase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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