ArticleThe Journal of biological chemistry2016
Complex Formation of Human Proelastases with Procarboxypeptidases A1 and A2.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Chymotrypsin B2 (CTRB2) Deletion Variant Induces Endoplasmic Reticulum Stress but does not Increase Risk for Chronic Pancreatitis.Pancreas · 2025Article
- Mouse model of PRSS1 p.R122H-related hereditary pancreatitis highlights context-dependent effect of autolysis-site mutation.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2023Article
- CELA3B immunostaining is a highly specific marker for acinar cell carcinoma of the pancreas.PloS one · 2023Article
- Novel p.G250A Mutation Associated with Chronic Pancreatitis Highlights Misfolding-Prone Region in Carboxypeptidase A1 (CPA1).International journal of molecular sciences · 2022Article
- Ambush predation and the origin of euprimates.Science advances · 2022Article
- Loss-of-function variant in chymotrypsin like elastase 3B (CELA3B) is associated with non-alcoholic chronic pancreatitis.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2022Article
- Diet evolution of carnivorous and herbivorous mammals in Laurasiatheria.BMC ecology and evolution · 2022Article
- Clinicopathological and Fecal Proteome Evaluations in 16 Dogs Presenting Chronic Diarrhea Associated with Lymphangiectasia.Veterinary sciences · 2021Article
- Molecular phyloecology suggests a trophic shift concurrent with the evolution of the first birds.Communications biology · 2021Article
- Mouse model suggests limited role for human mesotrypsin in pancreatitis.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2021Article
- Insights into Dietary Switch in Cetaceans: Evidence from Molecular Evolution of Proteinases and Lipases.Journal of molecular evolution · 2020Article
- Screening differentially expressed genes of pancreatic cancer between Mongolian and Han people using bioinformatics technology.BMC cancer · 2020Article
- Review
- Elastase 3B mutation links to familial pancreatitis with diabetes and pancreatic adenocarcinoma.The Journal of clinical investigation · 2019Article
- CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation.Nature genetics · 2019Article
- Article
- Detection of human elastase isoforms by the ScheBo Pancreatic Elastase 1 Test.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Overlapping Specificity of Duplicated Human Pancreatic Elastase 3 Isoforms and Archetypal Porcine Elastase 1 Provides Clues to Evolution of Digestive Enzymes.The Journal of biological chemistry · 2017Article
- Genetic Analysis of Human Chymotrypsin-Like Elastases 3A and 3B (CELA3A and CELA3B) to Assess the Role of Complex Formation between Proelastases and Procarboxypeptidases in Chronic Pancreatitis.International journal of molecular sciences · 2016Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
The pancreas secretes digestive proenzymes typically in their monomeric form. A notable exception is the ternary complex formed by proproteinase E, chymotrypsinogen C, and procarboxypeptidase A (proCPA) in cattle and other ruminants. In the human and pig pancreas binary complexes of proCPA with proelastases were found. To characterize complex formation among human pancreatic protease zymogens in a systematic manner, we performed binding experiments using recombinant proelastases CELA2A, CELA3A, and CELA3B; chymotrypsinogens CTRB1, CTRB2, CTRC, and CTRL1; and procarboxypeptidases CPA1, CPA2, and CPB1. We found that proCELA3B bound not only to proCPA1 (KD 43 nm) but even more tightly to proCPA2 (KD 18 nm), whereas proCELA2A bound weakly to proCPA1 only (KD 152 nm). Surprisingly, proCELA3A, which shares 92% identity with proCELA3B, did not form stable complexes due to the evolutionary replacement of Ala(241) with Gly. The polymorphic nature of position 241 in both CELA3A (∼4% Ala(241) alleles) and CELA3B (∼2% Gly(241) alleles) points to individual variations in complex formation. The functional effect of complex formation was delayed procarboxypeptidase activation due to increased affinity of the inhibitory activation peptide, whereas proelastase activation was unchanged. We conclude that complex formation among human pancreatic protease zymogens is limited to a subset of proelastases and procarboxypeptidases. Complex formation stabilizes the inhibitory activation peptide of procarboxypeptidases and thereby increases zymogen stability and controls activation.
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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.