Tripeptidyl peptidase: Difference between revisions

Latest revision as of 10:21, 17 May 2022

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].

Glycosylated tripeptidyl peptidase I dimer complex with sulfate, Zn+2 (grey), Ca+2 (green) and Cl- (green) ions, 3ee6

Drag the structure with the mouse to rotate

3D Structures of Tripeptidyl peptidase3D Structures of Tripeptidyl peptidase

Updated on 17-May-2022

ReferencesReferences

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky, Michal Harel, Joel L. Sussman

[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

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-[[Image:2d5l.png|left|200px|thumb|Crystal Structure of Tripeptidyl peptidase ([[2d5l]])]]
+<StructureSection load='' size='350' side='right' caption='Glycosylated tripeptidyl peptidase I dimer complex with sulfate, Zn+2 (grey), Ca+2 (green) and Cl- (green) ions, [[3ee6]]' scene='43/433127/Cv/5'>
-{{STRUCTURE_3ee6|  PDB=3ee6  | SIZE=400| SCENE= |right|CAPTION=Tripeptidyl peptidase [[3ee6]]}}
-[[Tripeptidyl peptidase]] (TPP) is an enzyme which cleaves N-terminal tripeptides from polypeptides.  TPP-I functions in lysosomes, TPP-II is part of the ubiquitin-proteasome pathway. The images at the left and at the right correspond to one representative TPP, ''i.e.'' the crystal structure of Pro-Tripeptidyl peptidase-IV from ''Porphyromonas gingivalis'' ([[2d5l]]).
+== Function ==
+[[Tripeptidyl peptidase]] or '''tripeptidyl aminopeptidase''' (TPP) is an enzyme which cleaves N-terminal tripeptides from polypeptides.<br />
+*  '''TPP-I''' functions in lysosomes<ref>PMID:29378960</ref>.<br />
+*  '''TPP-II''' is part of the ubiquitin-proteasome pathway. <br />
+*  '''TPP-IV''' is a serine exopeptidase which cleaves proline dipeptides from the N-terminus of polypeptides.
-{{TOC limit|limit=2}}
+== 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<ref>PMID:11589013</ref>.  TPP-II deficiency is linked to severe autoimmunity<ref>PMID:25414442</ref>.  TPP-II has central and peripheral roles in metabolism and hence in fat formation<ref>PMID:17932511</ref>.
+== Structural highlights ==
+TPP-I catalytic triad is the typical <scene name='43/433127/Cv/6'>Ser-Glu-Asp</scene> and the active site contains an <scene name='43/433127/Cv/7'>octahedrally coordinated Ca+2 ion</scene><ref>PMID:19038966</ref>.
+</StructureSection>
 == 3D Structures of Tripeptidyl peptidase ==
+Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+{{#tree:id=OrganizedByTopic|openlevels=0|
+*Tripeptidyl peptidase-I
-===TPP-I===
+**[[3ee6]] – TPP-I – human<br />
+**[[3edy]] – hTPP-I precursor residues 20-563<br />
-[[3ee6]] – TPP-I – human<br />
-[[3edy]] – hTPP-I precursor residues 20-563<br />
-===TPP-II===
-[[3lxu]] – TPP-II residues 463-770 – ''Drosophila melanogaster''<br />
-===TPP-IV===
+*Tripeptidyl peptidase-II
-[[2eep]] – PgPro-TPP-IV+inhibitor – ''Porphyromonas gingivalis''<br />
+**[[3lxu]] – TPP-II residues 463-770 – ''Drosophila melanogaster''<br />
-[[2d5l]] - PgPro-TPP-IV<br />
-[[2z3w]] - PgPro-TPP-IV (mutant)<br />
-[[2z3z]], [[2dcm]] - PgPro-TPP-IV (mutant)+inhibitor<br />
+*Tripeptidyl peptidase-IV
+**[[2eep]] – PgPro-TPP-IV+inhibitor – ''Porphyromonas gingivalis''<br />
+**[[2d5l]] - PgPro-TPP-IV<br />
+**[[2z3w]] - PgPro-TPP-IV (mutant)<br />
+**[[2z3z]] - PgPro-TPP-IV (mutant)+inhibitor<br />
+**[[2dcm]] - PgPro-TPP-IV (mutant) + substrate<br />
+}}
+== References ==
+<references/>
 [[Category:Topic Page]]