ArticlePloS one2013
Allosteric regulation of serine protease HtrA2 through novel non-canonical substrate binding pocket.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 37 citations in OpenAlex.
- cFLIP - An interacting partner and a novel substrate for pro-apoptotic serine protease HtrA2.Biochemistry and biophysics reports · 2024Article
- Structural basis of substrate recognition and allosteric activation of the proapoptotic mitochondrial HtrA2 protease.Nature communications · 2024Article
- Structural basis of protein substrate processing by human mitochondrial high-temperature requirement A2 protease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Interplay between HTRA1 and classical signalling pathways in organogenesis and diseases.Saudi journal of biological sciences · 2022Review
- Article
- Oligomeric assembly regulating mitochondrial HtrA2 function as examined by methyl-TROSY NMR.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A distinct concerted mechanism of structural dynamism defines activity of human serine protease HtrA3.The Biochemical journal · 2020Article
- Structural basis of inactivation of human counterpart of mouse motor neuron degeneration 2 mutant in serine protease HtrA2.Bioscience reports · 2018Article
- In Silico Studies in Drug Research Against Neurodegenerative Diseases.Current neuropharmacology · 2018Review
- Molecular motion regulates the activity of the Mitochondrial Serine Protease HtrA2.Cell death & disease · 2017Article
- Solution NMR Spectroscopy for the Study of Enzyme Allostery.Chemical reviews · 2016Review
- Distinct 3D Architecture and Dynamics of the Human HtrA2(Omi) Protease and Its Mutated Variants.PloS one · 2016Article
- Temperature dependent dynamics of DegP-trimer: A molecular dynamics study.Computational and structural biotechnology journal · 2015Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HtrA2, a trimeric proapoptotic serine protease is involved in several diseases including cancer and neurodegenerative disorders. Its unique ability to mediate apoptosis via multiple pathways makes it an important therapeutic target. In HtrA2, C-terminal PDZ domain upon substrate binding regulates its functions through coordinated conformational changes the mechanism of which is yet to be elucidated. Although allostery has been found in some of its homologs, it has not been characterized in HtrA2 so far. Here, with an in silico and biochemical approach we have shown that allostery does regulate HtrA2 activity. Our studies identified a novel non-canonical selective binding pocket in HtrA2 which initiates signal propagation to the distal active site through a complex allosteric mechanism. This non-classical binding pocket is unique among HtrA family proteins and thus unfolds a novel mechanism of regulation of HtrA2 activity and hence apoptosis.
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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.