Tripeptidyl peptidase

From Proteopedia

Glycosylated tripeptidyl peptidase I dimer complex with sulfate, Zn+2 (grey), Ca+2 (green) and Cl- (green) ions, 3ee6 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Tripeptidyl peptidase or tripeptidyl aminopeptidase (TPP) is an enzyme which cleaves N-terminal tripeptides from polypeptides. TPP-I functions in lysosomes[1]. TPP-II is part of the ubiquitin-proteasome pathway. TPP-IV is a serine exopeptidase which cleaves proline dipeptides from the N-terminus of polypeptides. Didease TPP-I participates in lysosomal turnover of proteins in pathological conditions associated with cell injury and its mutations cause the fatal neurodegenerative childhood neuronal ceroid lipofuscinosis[2]. TPP-II deficiency is linked to severe autoimmunity[3]. TPP-II has central and peripheral roles in metabolism and hence in fat formation[4]. Structural highlights TPP-I catalytic triad is the typical and the active site contains an [5].

3D Structures of Tripeptidyl peptidase

Updated on 17-May-2022

References

1. ↑ Sole-Domenech S, Rojas AV, Maisuradze GG, Scheraga HA, Lobel P, Maxfield FR. Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar Abeta by multiple endoproteolytic cleavages within the beta-sheet domain. Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):1493-1498. doi:, 10.1073/pnas.1719808115. Epub 2018 Jan 29. PMID:29378960 doi:http://dx.doi.org/10.1073/pnas.1719808115
2. ↑ Wisniewski KE, Kida E, Walus M, Wujek P, Kaczmarski W, Golabek AA. Tripeptidyl-peptidase I in neuronal ceroid lipofuscinoses and other lysosomal storage disorders. Eur J Paediatr Neurol. 2001;5 Suppl A:73-9. PMID:11589013
3. ↑ Stepensky P, Rensing-Ehl A, Gather R, Revel-Vilk S, Fischer U, Nabhani S, Beier F, Brummendorf TH, Fuchs S, Zenke S, Firat E, Pessach VM, Borkhardt A, Rakhmanov M, Keller B, Warnatz K, Eibel H, Niedermann G, Elpeleg O, Ehl S. Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency. Blood. 2015 Jan 29;125(5):753-61. doi: 10.1182/blood-2014-08-593202. Epub 2014, Nov 20. PMID:25414442 doi:http://dx.doi.org/10.1182/blood-2014-08-593202
4. ↑ McKay RM, McKay JP, Suh JM, Avery L, Graff JM. Tripeptidyl peptidase II promotes fat formation in a conserved fashion. EMBO Rep. 2007 Dec;8(12):1183-9. Epub 2007 Oct 12. PMID:17932511 doi:http://dx.doi.org/10.1038/sj.embor.7401086
5. ↑ Pal A, Kraetzner R, Gruene T, Grapp M, Schreiber K, Gronborg M, Urlaub H, Becker S, Asif AR, Gartner J, Sheldrick GM, Steinfeld R. Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis. J Biol Chem. 2009 Feb 6;284(6):3976-84. Epub 2008 Nov 26. PMID:19038966 doi:10.1074/jbc.M806947200