ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis.Nature communications · 2015Pooled it
- Human genetic and metabolite variation reveals that methylthioadenosine is a prognostic biomarker and an inflammatory regulator in sepsis.Science advances · 2017Trial
- APIP regulates the priming of canonical NLRP3 and non-canonical Caspase-11/4 inflammasomes by binding to TRAF6.Nature communications · 2025Article
- A novel pyroptosis-related gene signature exhibits distinct immune cells infiltration landscape in Wilms' tumor.BMC pediatrics · 2024Article
- Article
- Who Modifies the Modifiers: A High-Resolution View of the Genetic Modifiers of Cystic Fibrosis.American journal of respiratory and critical care medicine · 2023Article
- Values of a novel pyroptosis-related genetic signature in predicting outcome and immune status of pancreatic ductal adenocarcinoma.Gastroenterology report · 2022Article
- Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine.Genes · 2021Review
- Identification and Validation of a Novel Pyroptosis-Related Gene Signature for Prognosis Prediction in Soft Tissue Sarcoma.Frontiers in genetics · 2021Article
- An unusual metal-bound 4-fluorothreonine transaldolase from Streptomyces sp. MA37 catalyses promiscuous transaldol reactions.Applied microbiology and biotechnology · 2020Article
- Advances of Zinc Signaling Studies in Prostate Cancer.International journal of molecular sciences · 2020Review
- Cardioprotective role of APIP in myocardial infarction through ADORA2B.Cell death & disease · 2019Article
- The methionine salvage pathway-involving ADI1 inhibits hepatoma growth by epigenetically altering genes expression via elevating S-adenosylmethionine.Cell death & disease · 2019Article
- Revisiting the methionine salvage pathway and its paralogues.Microbial biotechnology · 2019Article
- Airway Mucosal Host Defense Is Key to Genomic Regulation of Cystic Fibrosis Lung Disease Severity.American journal of respiratory and critical care medicine · 2018Article
- Regulatory dynamics of 11p13 suggest a role for EHF in modifying CF lung disease severity.Nucleic acids research · 2017Article
- Molecular heterogeneity in the novel fusion geneOncology letters · 2017Article
- Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.PloS one · 2017Article
- APIP, an ERBB3-binding partner, stimulates erbB2-3 heterodimer formation to promote tumorigenesis.Oncotarget · 2016Article
- Novel variation at chr11p13 associated with cystic fibrosis lung disease severity.Human genome variation · 2016Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
APIP, Apaf-1 interacting protein, has been known to inhibit two main types of programmed cell death, apoptosis and pyroptosis, and was recently found to be associated with cancers and inflammatory diseases. Distinct from its inhibitory role in cell death, APIP was also shown to act as a 5-methylthioribulose-1-phosphate dehydratase, or MtnB, in the methionine salvage pathway. Here we report the structural and enzymatic characterization of human APIP as an MtnB enzyme with a Km of 9.32 μM and a Vmax of 1.39 μmol min(-1) mg(-1). The crystal structure was determined at 2.0-Å resolution, revealing an overall fold similar to members of the zinc-dependent class II aldolase family. APIP/MtnB exists as a tetramer in solution and exhibits an assembly with C4 symmetry in the crystal lattice. The pocket-shaped active site is located at the end of a long cleft between two adjacent subunits. We propose an enzymatic reaction mechanism involving Glu139* as a catalytic acid/base, as supported by enzymatic assay, substrate-docking study, and sequence conservation analysis. We explored the relationship between two distinct functions of APIP/MtnB, cell death inhibition, and methionine salvage, by measuring the ability of enzymatic mutants to inhibit cell death, and determined that APIP/MtnB functions as a cell death inhibitor independently of its MtnB enzyme activity for apoptosis induced by either hypoxia or etoposide, but dependently for caspase-1-induced pyroptosis. Our results establish the structural and biochemical groundwork for future mechanistic studies of the role of APIP/MtnB in modulating cell death and inflammation and in the development of related diseases.
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