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PDBsum entry 1r60

Go to PDB code: 
protein ligands metals links
Hydrolase PDB id
1r60
Jmol
Contents
Protein chain
368 a.a.
Ligands
IVA-PHI-TYB
Metals
_CA
Theoretical model
PDB id:
1r60
Name: Hydrolase
Title: A homology-derived model of human tripeptidyl-peptidase i (cln2)
Structure: Tripeptidyl-peptidase i. Chain: a. Synonym: cln2. Pseudoiodotyrostatin. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Synthetic: yes. Other_details: chemically synthesized
Authors: A.Wlodawer,S.R.Durell,M.Li,H.Oyama,K.Oda,B.M.Dunn
Key ref: A.Wlodawer et al. (2003). A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases. BMC Struct Biol, 3, 8. PubMed id: 14609438
Date:
14-Oct-03     Release date:   28-Oct-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O14773  (TPP1_HUMAN) -  Tripeptidyl-peptidase 1
Seq:
Struc:
 
Seq:
Struc:
563 a.a.
368 a.a.
Key:    PfamA domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.3.4.14.9  - Tripeptidyl-peptidase I.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Release of an N-terminal tripeptide from a polypeptide, but also endopeptidase activity.

 

 
BMC Struct Biol 3:8 (2003)
PubMed id: 14609438  
 
 
A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases.
A.Wlodawer, S.R.Durell, M.Li, H.Oyama, K.Oda, B.M.Dunn.
 
  ABSTRACT  
 
BACKGROUND: Tripeptidyl-peptidase I, also known as CLN2, is a member of the family of sedolisins (serine-carboxyl peptidases). In humans, defects in expression of this enzyme lead to a fatal neurodegenerative disease, classical late-infantile neuronal ceroid lipofuscinosis. Similar enzymes have been found in the genomic sequences of several species, but neither systematic analyses of their distribution nor modeling of their structures have been previously attempted. RESULTS: We have analyzed the presence of orthologs of human CLN2 in the genomic sequences of a number of eukaryotic species. Enzymes with sequences sharing over 80% identity have been found in the genomes of macaque, mouse, rat, dog, and cow. Closely related, although clearly distinct, enzymes are present in fish (fugu and zebra), as well as in frogs (Xenopus tropicalis). A three-dimensional model of human CLN2 was built based mainly on the homology with Pseudomonas sp. 101 sedolisin. CONCLUSION: CLN2 is very highly conserved and widely distributed among higher organisms and may play an important role in their life cycles. The model presented here indicates a very open and accessible active site that is almost completely conserved among all known CLN2 enzymes. This result is somehow surprising for a tripeptidase where the presence of a more constrained binding pocket was anticipated. This structural model should be useful in the search for the physiological substrates of these enzymes and in the design of more specific inhibitors of CLN2.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20680390 A.L.Getty, and D.A.Pearce (2011).
Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function.
  Cell Mol Life Sci, 68, 453-474.  
20340139 M.Walus, E.Kida, and A.A.Golabek (2010).
Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I.
  Hum Mutat, 31, 710-721.  
19038966 A.Pal, R.Kraetzner, T.Gruene, M.Grapp, K.Schreiber, M.Grønborg, H.Urlaub, S.Becker, A.R.Asif, J.Gärtner, G.M.Sheldrick, and R.Steinfeld (2009).
Structure of Tripeptidyl-peptidase I Provides Insight into the Molecular Basis of Late Infantile Neuronal Ceroid Lipofuscinosis.
  J Biol Chem, 284, 3976-3984.
PDB code: 3ee6
19038967 J.Guhaniyogi, I.Sohar, K.Das, A.M.Stock, and P.Lobel (2009).
Crystal Structure and Autoactivation Pathway of the Precursor Form of Human Tripeptidyl-peptidase 1, the Enzyme Deficient in Late Infantile Ceroid Lipofuscinosis.
  J Biol Chem, 284, 3985-3997.
PDB code: 3edy
18411270 A.A.Golabek, N.Dolzhanskaya, M.Walus, K.E.Wisniewski, and E.Kida (2008).
Prosegment of tripeptidyl peptidase I is a potent, slow-binding inhibitor of its cognate enzyme.
  J Biol Chem, 283, 16497-16504.  
18283468 M.Elleder, L.Dvoráková, L.Stolnaja, H.Vlásková, H.Hůlková, R.Druga, H.Poupetová, E.Kostálová, and J.Mikulástík (2008).
Atypical CLN2 with later onset and prolonged course: a neuropathologic study showing different sensitivity of neuronal subpopulations to TPP1 deficiency.
  Acta Neuropathol, 116, 119-124.  
16895480 A.A.Golabek, and E.Kida (2006).
Tripeptidyl-peptidase I in health and disease.
  Biol Chem, 387, 1091-1099.  
16704427 A.Okubo, M.Li, M.Ashida, H.Oyama, A.Gustchina, K.Oda, B.M.Dunn, A.Wlodawer, and T.Nakayama (2006).
Processing, catalytic activity and crystal structures of kumamolisin-As with an engineered active site.
  FEBS J, 273, 2563-2576.
PDB codes: 1zvj 1zvk
16339154 Y.Tian, I.Sohar, J.W.Taylor, and P.Lobel (2006).
Determination of the substrate specificity of tripeptidyl-peptidase I using combinatorial peptide libraries and development of improved fluorogenic substrates.
  J Biol Chem, 281, 6559-6572.  
15965709 S.E.Mole, R.E.Williams, and H.H.Goebel (2005).
Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses.
  Neurogenetics, 6, 107-126.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.