ArticleBMC structural biology2003
A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases.
Article in BMC structural biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 44 citations in OpenAlex.
- Adverse Reactions to the Orphan Drug Cerliponase Alfa in the Treatment of Neurolipofuscinosis Type 2 (CLN2).Pharmaceuticals (Basel, Switzerland) · 2024Article
- Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys.Toxicology reports · 2023Article
- Autocrine GMCSF Signaling Contributes to Growth of HER2Cancer research · 2021Article
- Article
- Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy.Therapeutics and clinical risk management · 2020Review
- A tripeptidyl peptidase 1 is a binding partner of the Golgi pH regulator (GPHR) inDisease models & mechanisms · 2017Article
- Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function.Cellular and molecular life sciences : CMLS · 2011Review
- Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis.The Journal of biological chemistry · 2009Article
- Atypical CLN2 with later onset and prolonged course: a neuropathologic study showing different sensitivity of neuronal subpopulations to TPP1 deficiency.Acta neuropathologica · 2008Article
- Prosegment of tripeptidyl peptidase I is a potent, slow-binding inhibitor of its cognate enzyme.The Journal of biological chemistry · 2008Article
- Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses.Neurogenetics · 2005Review
- The genetic spectrum of human neuronal ceroid-lipofuscinoses.Brain pathology (Zurich, Switzerland) · 2004Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTripeptidyl-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.
resultsWe 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.
conclusionCLN2 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.