title: Comparative structural analysis of the caspase family with other clan CD cysteine peptidases.
abstract: Clan CD forms a structural group of cysteine peptidases, containing seven individual families and two subfamilies of structurally related enzymes. Historically, it is most notable for containing the mammalian caspases, on which the structures of the clan were founded. Interestingly, the caspase family is split into two subfamilies: the caspases, and a second subfamily containing both the paracaspases and the metacaspases. Structural data are now available for both the paracaspases and the metacaspases, allowing a comprehensive structural analysis of the entire caspase family. In addition, a relative plethora of structural data has recently become available for many of the other families in the clan, allowing both the structures and the structure-function relationships of clan CD to be fully explored. The present review compares the enzymes in the caspase subfamilies with each other, together with a comprehensive comparison of all the structural families in clan CD. This reveals a diverse group of structures with highly conserved structural elements that provide the peptidases with a variety of substrate specificities and activation mechanisms. It also reveals conserved structural elements involved in substrate binding, and potential autoinhibitory functions, throughout the clan, and confirms that the metacaspases are structurally diverse from the caspases (and paracaspases), suggesting that they should form a distinct family of clan CD peptidases.
authors.affiliation: *Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: McLuskey
authors.affiliation: *Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Mottram
mesh_terms: D000818:Animals; D001665:Binding Sites; D020169:Caspases / Q000737:chemistry*; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D004792:Enzyme Precursors; D007527:Isoenzymes; D008024:Ligands; D020169:Caspases; D003546:Cysteine Endopeptidases