title: CBS domains: structure, function, and pathology in human proteins.
abstract: The cystathionine-beta-synthase (CBS) domain is an evolutionarily conserved protein domain that is present in the proteome of archaebacteria, prokaryotes, and eukaryotes. CBS domains usually come in tandem repeats and are found in cytosolic and membrane proteins performing different functions (metabolic enzymes, kinases, and channels). Crystallographic studies of bacterial CBS domains have shown that two CBS domains form an intramolecular dimeric structure (CBS pair). Several human hereditary diseases (homocystinuria, retinitis pigmentosa, hypertrophic cardiomyopathy, myotonia congenital, etc.) can be caused by mutations in CBS domains of, respectively, cystathionine-beta-synthase, inosine 5'-monophosphate dehydrogenase, AMP kinase, and chloride channels. Despite their clinical relevance, it remains to be established what the precise function of CBS domains is and how they affect the structural and/or functional properties of an enzyme, kinase, or channel. Depending on the protein in which they occur, CBS domains have been proposed to affect multimerization and sorting of proteins, channel gating, and ligand binding. However, recent experiments revealing that CBS domains can bind adenosine-containing ligands such ATP, AMP, or S-adenosylmethionine have led to the hypothesis that CBS domains function as sensors of intracellular metabolites.
authors.affiliation: Laboratory of Physiology, K.U. Leuven, Campus Gasthuisberg O&N, Herestraat 49, B-3000 Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Ignoul
authors.forename: Jan
authors.initials: J
authors.lastname: Eggermont
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D018118:Chloride Channels; D009097:Multienzyme Complexes; D007168:IMP Dehydrogenase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D003541:Cystathionine beta-Synthase