Phosphorylase kinase (PhK) is a large hexadecameric enzyme consisting of four copies of four subunits: (alphabetagammadelta)4. An intrinsic calmodulin (CaM, the delta subunit) binds directly to the gamma protein kinase chain. The interaction site of CaM on gamma has been localized to a C-terminal extension of the kinase domain. Two 25-mer peptides derived from this region, PhK5 and PhK13, were identified previously as potential CaM-binding sites. Complex formation between Ca2+/CaM with these two peptides was characterized using analytical gel filtration and NMR methods. NMR chemical shift perturbation studies showed that while PhK5 forms a robust complex with Ca2+/CaM, no interactions with PhK13 were observed. 15N relaxation characteristics of Ca2+/CaM and Ca2+/CaM/PhK5 complexes were compared with the experimentally determined structures of several Ca2+/CaM/peptide complexes. Good fits were observed between Ca2+/CaM/PhK5 and three structures: Ca2+/CaM complexes with peptides from endothelial nitric oxide synthase, with smooth muscle myosin light chain kinase and CaM kinase I. We conclude that the PhK5 site is likely to have a direct role in Ca2+-regulated control of PhK activity through the formation of a classical 'compact' CaM complex.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1742-4658.2005.04591.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Glycogen storage disorder types IX: the mutation spectrum and ethnic distribution.
Orphanet J Rare Dis
December 2024
Assistant Professor of Cellular and Molecular Medicine, Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Khalili St., Research Tower, Seventh Floor, Shiraz, Iran.
Glycogen storage disorders (GSD) GSD-IX are characterized by deficiencies in muscular and/or hepatic phosphorylase enzymes. GSD type IX za is an X-linked disorder, while IXb and IXc are autosomal recessive disorders resulting from pathogenic variants in the genes encoding the Phosphorylase b Kinase regulatory subunit alpha (PHKA), beta (PHKB), and gamma (PHKG), respectively. Despite progress in understanding these diseases, there are still unclear questions regarding their clinical manifestations, genetic variations, and the relationship between genotype and phenotype.
View Article and Find Full Text PDFTBK1 Reprograms Metabolism in Breast Cancer: An Integrated Omics Approach.
J Proteome Res
December 2024
Department of Biotechnology, Birla Institute of Technology and Science Pilani (BITS Pilani) - Dubai Campus, Academic City, Dubai, P.O. Box 345055, United Arab Emirates.
Metabolic rewiring is required for cancer cells to survive in harsh microenvironments and is considered to be a hallmark of cancer. Specific metabolic adaptations are required for a tumor to become invasive and metastatic. Cell division and metabolism are inherently interconnected, and several cell cycle modulators directly regulate metabolism.
View Article and Find Full Text PDFIsatin-1,2,3-triazole derivatives: Synthesis, molecular docking and evaluation against acute experimental toxoplasmosis.
Acta Trop
December 2024
Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, 21577, Egypt.
Toxoplasmosis remains a challenge for both public health and animal husbandry which created a constant demand to develop novel compounds using innovative methods. To join this relentless quest for an ideal chemotherapeutic agent, herein, we developed newly synthesized isatin-1,2,3-triazole derivatives. Three compounds (5a, 5b and 5c) were synthesized, characterized, loaded on chitosan nanoparticles (CNPs) and then evaluated accordingly.
View Article and Find Full Text PDFProgressive liver disease and dysregulated glycogen metabolism in murine GSD IX γ2 models human disease.
Mol Genet Metab
December 2024
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. Electronic address:
Hepatic glycogen storage disease type IX γ2 (GSD IX γ2) is a severe, liver-specific subtype of GSD IX. While all patients with hepatic GSD IX present with similar symptoms, over 95 % of patients with GSD IX γ2 progress to liver fibrosis and cirrhosis. Despite disease severity, the long-term natural history of GSD IX γ2 liver disease progression is not known.
View Article and Find Full Text PDFLicochalcone D from Improves High-Glucose-Induced Insulin Resistance in Hepatocytes.
Int J Mol Sci
September 2024
Personalized Diet Research Group, Korea Food Research Institute (KFRI), Wanju 55365, Republic of Korea.
Article Synopsis
- The study explores how licochalcone D (LicoD), derived from certain plants, can enhance glucose metabolism in liver cells (AML12) that are insulin resistant due to high glucose levels.
- Researchers found that both hot water and ethanol extracts containing LicoD increased glucose uptake and improved genetic expression related to glucose metabolism in these cells.
- The therapeutic effects of LicoD were linked to the activation of key biological pathways that reduce insulin resistance and enhance mitochondrial function, suggesting its potential as a treatment for related metabolic disorders.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!