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Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
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Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

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Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
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Phosphorylation01:02

Phosphorylation

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The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
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cAMP-dependent Protein Kinase Pathways01:25

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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
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Identification of Kinase-substrate Pairs Using High Throughput Screening
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KinFams: De-Novo Classification of Protein Kinases Using CATH Functional Units.

Tolulope Adeyelu1,2, Nicola Bordin1, Vaishali P Waman1

  • 1Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, UK.

Biomolecules
|February 25, 2023
PubMed
Summary
This summary is machine-generated.

We developed a new method to functionally classify protein kinases, identifying 28 druggable human kinase families. This classification aids in discovering new therapeutic targets for human diseases.

Keywords:
KinBase classificationKinFamsfunctional familiesprotein kinases

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Area of Science:

  • Biochemistry
  • Bioinformatics
  • Structural Biology

Background:

  • Protein kinases are crucial drug targets, second only to G-protein coupled receptors.
  • Existing classifications primarily focus on evolutionary relationships, lacking functional coherence.

Purpose of the Study:

  • To develop a systematic classification of protein kinase functional families (FunFams).
  • To identify druggable kinase families for therapeutic target discovery.

Main Methods:

  • Utilized the FunFam-MARC protocol, integrating multi-domain architectures and specificity-determining residues.
  • Classified kinase sequences from over 10,000 organisms into 2210 kinase functional families (KinFams).

Main Results:

  • The FunFam-MARC classification demonstrates higher functional coherence (EC annotations) than existing methods like KinBase.
  • Identified 28 druggable human KinFams enriched with clinically approved drugs.
  • Provided 3D structures and conserved residue information for KinFams.

Conclusions:

  • The FunFam-MARC protocol offers a comprehensive and functionally coherent classification of protein kinases.
  • Druggable KinFams represent promising candidates for developing new therapeutics.
  • The associated data resources facilitate further research in kinase-targeted drug discovery.