title: The CATH hierarchy revisited-structural divergence in domain superfamilies and the continuity of fold space.
abstract: This paper explores the structural continuum in CATH and the extent to which superfamilies adopt distinct folds. Although most superfamilies are structurally conserved, in some of the most highly populated superfamilies (4% of all superfamilies) there is considerable structural divergence. While relatives share a similar fold in the evolutionary conserved core, diverse elaborations to this core can result in significant differences in the global structures. Applying similar protocols to examine the extent to which structural overlaps occur between different fold groups, it appears this effect is confined to just a few architectures and is largely due to small, recurring super-secondary motifs (e.g., alphabeta-motifs, alpha-hairpins). Although 24% of superfamilies overlap with superfamilies having different folds, only 14% of nonredundant structures in CATH are involved in overlaps. Nevertheless, the existence of these overlaps suggests that, in some regions of structure space, the fold universe should be seen as more continuous.
authors.affiliation: Institute of Structural and Molecular Biology, University College London, London, UK. cuff@biochem.ucl.ac.uk
authors.forename: Alison
authors.initials: A
authors.lastname: Cuff
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Redfern
authors.forename: Lesley
authors.initials: L
authors.lastname: Greene
authors.forename: Ian
authors.initials: I
authors.lastname: Sillitoe
authors.forename: Tony
authors.initials: T
authors.lastname: Lewis
authors.forename: Mark
authors.initials: M
authors.lastname: Dibley
authors.forename: Adam
authors.initials: A
authors.lastname: Reid
authors.forename: Frances
authors.initials: F
authors.lastname: Pearl
authors.forename: Tim
authors.initials: T
authors.lastname: Dallman
authors.forename: Annabel
authors.initials: A
authors.lastname: Todd
authors.forename: Richard
authors.initials: R
authors.lastname: Garratt
authors.forename: Janet
authors.initials: J
authors.lastname: Thornton
authors.forename: Christine
authors.initials: C
authors.lastname: Orengo
mesh_terms: D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000145:classification
chemical_list: D011506:Proteins
references.citation: J Mol Biol. 1995 Apr 7;247(4):536-40
references.pmid: 7723011
references.citation: Annu Rev Biochem. 2005;74:867-900
references.pmid: 15954844
references.citation: J Struct Biol. 2001 May-Jun;134(2-3):167-85
references.pmid: 11551177
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):373-8
references.pmid: 15630082
references.citation: Bioinformatics. 2003 Jul 1;19(10):1275-83
references.pmid: 12835272
references.citation: Nucleic Acids Res. 2006 Feb 15;34(3):1066-80
references.pmid: 16481312
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D308-13
references.pmid: 17098927
references.citation: Structure. 1997 Aug 15;5(8):1093-108
references.pmid: 9309224
references.citation: Bioinformatics. 2001 Feb;17(2):200-1
references.pmid: 11238081
references.citation: J Mol Biol. 2003 Feb 7;326(1):317-36
references.pmid: 12547212
references.citation: Proteins. 2005 May 15;59(3):603-15
references.pmid: 15768405
references.citation: Curr Opin Struct Biol. 2008 Apr;18(2):170-7
references.pmid: 18328690
references.citation: Structure. 1993 Oct 15;1(2):105-20
references.pmid: 8069624
references.citation: Bioinformatics. 2007 Sep 15;23(18):2353-60
references.pmid: 17709341
references.citation: Bioinformatics. 2001 Jan;17(1):63-72
references.pmid: 11222263
references.citation: J Mol Biol. 2005 Mar 4;346(4):1173-88
references.pmid: 15701525
references.citation: Genome Biol. 2004;5(5):107
references.pmid: 15128436
references.citation: Proteins. 2005 Jan 1;58(1):166-79
references.pmid: 15521074
references.citation: Nucleic Acids Res. 2004 Oct 14;32(18):5539-45
references.pmid: 15486203
references.citation: Genome Res. 2002 Mar;12(3):503-14
references.pmid: 11875040
references.citation: Bioinformatics. 2005 Apr 15;21(8):1308-10
references.pmid: 15604105
references.citation: PLoS Comput Biol. 2007 Nov;3(11):e237
references.pmid: 18052542
references.citation: BMC Evol Biol. 2005 Feb 03;5:10
references.pmid: 15691378
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W249-51
references.pmid: 15980462
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: EMBO J. 1986 Apr;5(4):823-6
references.pmid: 3709526
references.citation: Proteins. 2001 Feb 15;42(3):332-44
references.pmid: 11151005
references.citation: PLoS Comput Biol. 2007 Nov;3(11):e232
references.pmid: 18052539
references.citation: Protein Sci. 1998 Nov;7(11):2469-71
references.pmid: 9828015
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D291-7
references.pmid: 17135200
references.citation: J Mol Biol. 1976 Jul 25;105(1):75-95
references.pmid: 186608
references.citation: Bioinformatics. 2003 Sep 22;19(14):1748-59
references.pmid: 14512345
references.citation: Curr Biol. 1993 Mar;3(3):141-8
references.pmid: 15335781
references.citation: Nature. 1994 Dec 15;372(6507):631-4
references.pmid: 7990952
references.citation: Curr Opin Struct Biol. 2006 Jun;16(3):393-8
references.pmid: 16678402
references.citation: J Mol Biol. 2005 May 20;348(5):1235-60
references.pmid: 15854658
references.citation: Bioinformatics. 2008 Mar 15;24(6):870-1
references.pmid: 18218654
references.citation: J Mol Biol. 2006 Jul 14;360(3):725-41
references.pmid: 16780872
references.citation: J Struct Biol. 2001 May-Jun;134(2-3):191-203
references.pmid: 11551179
references.citation: Acta Crystallogr D Biol Crystallogr. 1998 Nov 1;54(Pt 6 Pt 1):1147-54
references.pmid: 10089491
references.citation: J Mol Biol. 2002 Nov 8;323(5):909-26
references.pmid: 12417203