ArticleProceedings of the National Academy of Sciences of the United States of America2005
Structure of human carboxypeptidase A4 with its endogenous protein inhibitor, latexin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 104 citations in OpenAlex.
- Review
- Molecularly stratified hypothalamic astrocytes are cellular foci for obesity.Research square · 2024Article
- Angiopoietin-1 promotes triple-negative breast cancer cell proliferation by upregulating carboxypeptidase A4.Acta biochimica et biophysica Sinica · 2023Article
- Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1.Cell reports · 2023Article
- Isolation and Characterization of NpCI, a New Metallocarboxypeptidase Inhibitor from the Marine SnailMarine drugs · 2023Article
- Comprehensive Analysis of CPA4 as a Poor Prognostic Biomarker Correlated with Immune Cells Infiltration in Bladder Cancer.Biology · 2021Article
- β-Strand-mediated interactions of protein domains.Proteins · 2020Article
- Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling.Bioscience reports · 2020Article
- Downregulation of CPA4 inhibits non small-cell lung cancer growth by suppressing the AKT/c-MYC pathway.Molecular carcinogenesis · 2019Article
- Characterization, Recombinant Production and Structure-Function Analysis of NvCI, A Picomolar Metallocarboxypeptidase Inhibitor from the Marine SnailMarine drugs · 2019Article
- De Novo Structural Pattern Mining in Cellular Electron Cryotomograms.Structure (London, England : 1993) · 2019Article
- The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy.Scientific reports · 2019Article
- Structure of mammalian plasma fetuin-B and its mechanism of selective metallopeptidase inhibition.IUCrJ · 2019Article
- Bayesian Weighing of Electron Cryo-Microscopy Data for Integrative Structural Modeling.Structure (London, England : 1993) · 2019Article
- Crystal structure and mechanism of human carboxypeptidase O: Insights into its specific activity for acidic residues.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice.Stem cell reports · 2017Article
- Revealing Glycoproteins in the Secretome of MCF-7 Human Breast Cancer Cells.BioMed research international · 2015Article
- Latexin inhibits the proliferation of CD133+ miapaca-2 pancreatic cancer stem-like cells.World journal of surgical oncology · 2014Article
- Structural basis for the recognition of muramyltripeptide by Helicobacter pylori Csd4, a D,L-carboxypeptidase controlling the helical cell shape.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Latexin sensitizes leukemogenic cells to gamma-irradiation-induced cell-cycle arrest and cell death through Rps3 pathway.Cell death & disease · 2014Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The only endogenous protein inhibitor known for metallocarboxypeptidases (MCPs) is latexin, a 25-kDa protein discovered in the rat brain. Latexin, alias endogenous carboxypeptidase inhibitor, inhibits human CPA4 (hCPA4), whose expression is induced in prostate cancer cells after treatment with histone deacetylase inhibitors. hCPA4 is a member of the A/B subfamily of MCPs and displays the characteristic alpha/beta-hydrolase fold. Human latexin consists of two topologically equivalent subdomains, reminiscent of cystatins, consisting of an alpha-helix enveloped by a curved beta-sheet. These subdomains are packed against each other through the helices and linked by a connecting segment encompassing a third alpha-helix. The enzyme is bound at the interface of these subdomains. The complex occludes a large contact surface but makes rather few contacts, despite a nanomolar inhibition constant. This low specificity explains the flexibility of latexin in inhibiting all vertebrate A/B MCPs tested, even across species barriers. In contrast, modeling studies reveal why the N/E subfamily of MCPs and invertebrate A/B MCPs are not inhibited. Major differences in the loop segments shaping the border of the funnel-like access to the protease active site impede complex formation with latexin. Several sequences ascribable to diverse tissues and organs have been identified in vertebrate genomes as being highly similar to latexin. They are proposed to constitute the latexin family of potential inhibitors. Because they are ubiquitous, latexins could represent for vertebrate A/B MCPs the counterparts of tissue inhibitors of metalloproteases for matrix metalloproteinases.
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