Post on 03-Apr-2015
SCOP & CATH
Dr. M.I. Hassan
1. Protein Data Bank (PDB)
• Protein Data Bank: maintained by the Research Collaboratory for Structural Bioinformatics (RCSB)
• http://www.rcsb.org/pdb/– 30060 Structures 15-Mar-2005– 27570 Structures 05-Oct-2004– 23997 Structures 20-Jan-2004– 62787 Structures 20-Jan-2010
– Also contains structures of other bio-macromolecules: DNA, carbohydrates and protein-DNA complexes.
PDB Content Growth
Growth Of Unique Folds Per Year As Defined By SCOP
Growth Of Unique Topologies Per Year As Defined By CATH
Alternative Source of Structure: NCBI
Free Software for Protein Structure Visualization
• RASMOL: available for all platforms http://www.openrasmol.org
• Swiss PDB Viewer: from Swiss-Prot http://www.expasy.ch/spdbv/
• Chemscape Chime Plug-in: for PC and Mac http://www.mdl.com/downloads/downloadable/index.jsp
• YASARA: http://www.yasara.org/
• MOLMOL: MOLecule analysis and MOLecule display
http://129.132.45.141/wuthrich/software/molmol/index.html
• SCOP: Structural Classification of Proteins University of Cambridge, UK
http://scop.mrc-lmb.cam.ac.uk/scop/Hyperlink in Singapore: http://scop.bic.nus.edu.sg/
• CATH: Class—Architecture—Topology--Homologous SuperfamilySequence family
University College London, UKhttp://www.biochem.ucl.ac.uk/bsm/cath/
Hierarchical classification of protein domains: SCOP & CATH
Proteins adopt a limited number of topologiesMore than 50,000 sequences fold into ~1000 unique folds.
Homologous sequences have similar structures Usually, when sequence identity>30%, proteins adopt the same fold. Even in the absence of sequence homology, some folds are preferred by vastly different sequences.
The “active site” is highly conservedA subset of functionally critical residues are found to be conserved even the folds are varied.
Basis for protein classification
The hierarchy in SCOP
Root
Class
Fold
Superfamily
Family
Protein
Clear evolutionary relationship
Probable common ancestry
Have the same major secondary structure & topological connections
5 classes: All-, All-β, / β, + β, multi-domain
How many unique folds do organisms use to express functions?
Sequence space> 50,000
Conformationalspace
~1,000 ???????
Many sequences to form one unique fold
0
10000
20000
30000
40000
50000
60000
70000
80000
90000
1986
1988
1990
1992
1994
1996
1998
2000
No
of
Seq
uen
ces
0
2000
4000
6000
8000
10000
12000
No
. o
f S
tru
ctu
res
and
Fo
ldsSequences
Structures
Folds
Growth of Protein Databases
• University of Cambridge, UK: http://scop.mrc-lmb.cam.ac.uk/scop/– mirrored at Singapore: http://scop.bic.nus.edu.sg/– contains PDB entries grouped hierachically by:
• Structural class, • Fold,• Superfamily,• Family,• Individual member
(domain-based)
Structural Classification of Proteins SCOP
• Family
Structural Classification of Proteins SCOP
• Proteins are clustered together into families on the basis of one of two criteria that imply their having a common evolutionary origin:
• All proteins that have residue identities of 30% and greater;
• Proteins with lower sequence identities but whose functions and structures are very similar
Example, globins with sequence identities of 15%.
• Superfamily
Structural Classification of Proteins SCOP
• Families, whose proteins have low sequence identities but whose structures and, in many cases, functional features suggest that a common evolutionary origin is probable, are placed together in superfamilies
• Example, actin, the ATPase domain of the heat-shock protein and hexokinase
• Fold
Structural Classification of Proteins SCOP
• Superfamilies and families are defined as having a common fold if their proteins have same major secondary structures in same arrangement with the same topological connections.
Structural Classification of Proteins SCOP
• Class– For convenience of users, the different folds have been grouped into
classes. Most of the folds are assigned to one of a few structural classes on the basis of the secondary structures of which they composed
SCOP Class: All- topologies
ferritin cytochrome b-562
SCOP Class: All- topologies
SCOP Class: All- topologies
SCOP Class: All- topologies
sandwiches -barrels
SCOP Class: All- topologies
SCOP Class: Topologies
horseshoe
barrels
SCOP Class: Topologies
SCOP Class: Topologies
SCOP Class: Alpha+Beta Topologies
SCOP Class: Alpha+Beta Topologies
Ubiquitin
1ubi
Ubiquitin
1ubi
Ubiquitin
1ubi
Ubiquitin
1ubi
CATH database
Orengo et al. CATH-a hierarchical classification of protein domain structures (1997) Structure 5, 1093-1108
Sequence identity >30% the same overall foldSequence identity >70% the same overall fold
+ the similar function
CATH: Class—Architecture—Topology--Homologous Superfamily--Sequence family
http://www.biochem.ucl.ac.uk/bsm/cath/
ClassClass
ArchitectureArchitecture
TopologyTopology
Homologous Homologous SuperfamilySuperfamily
SequenceSequence
3 classes: Mainly-, Mainly-β, -β
Classified based on sequence identity
Share a common ancestor
Both the overall shape & connectivity of secondary structure
Overall shape as determined by orientations of secondary structures
The hierarchy in CATH
CATH databaseClassDerived from secondary structure content, is assigned for more than 90% of protein structures automatically.
ArchitectureDescribes the gross orientation of secondary structures, independent of connectivities, is currently assigned manually.
Topology Clusters structures according to their topological connections and numbers of secondary structures.
Homologous superfamilies Cluster proteins with highly similar structures and functions. The assignments of structures to topology families and homologous superfamilies are made by sequence and structure comparisons.
Sequence familiesStructures within each H-level are further clustered on sequence identity. Domains clustered in the same sequence families have sequence identities >35%.
Non-identical sequence domains, Identical sequence domains, Domains
CATH database
The class (C), architecture (A) and topology (T) levels in the CATH database
Class
Architecture
Topology
The class (C), architecture (A) and topology (T) levels in the CATH database
Homologous Superfamily
CATH – architecturesCATH – architectures
CATH – architectures (cont.)CATH – architectures (cont.)
The protein structure universe in the PDB (1997) by a CATH wheel
The distribution of non-homologous structures (i.e. a single representative from each homologous superfamily at the H-level in CATH) amongst the different classes (C), architectures (A) and fold families (T) in the CATH database.
SCOP / CATH -> DALI
SCOP & CATHSCOP & CATH
• Hierarchical and based on abstractions• Include some manual aspects and are curated by
experts in the field of protein structure
Presentation of results of computer classification, where the methods that underlie the classification remain
internal
Structure comparison
Dali
DALI
anti parallel barrel
meander
More information about DALI
Touring protein fold space with Dali/FSSP: Liisa Holm and Chris Sander
Comparing protein structures in 3D
Compare 3D protein structures by Dali http://www.ebi.ac.uk/dali/
• The FSSP database (Fold classification based on Structure-Structure alignment of Proteins) is based on exhaustive all-against-all 3D structure comparison of protein structures currently in the Protein Data Bank (PDB).
• The classification and alignments are automatically maintained and continuously updated using the Dali search engine.
Dali Domain Dictionary
• Structural domains are delineated automatically using the criteria of recurrence and compactness. Each domain is assigned a Domain Classification number DC_l_m_n_p , where:
l - fold space attractor region
m - globular folding topology
n - functional family
p - sequence family
Compare 3D protein structures by Dali http://www.ebi.ac.uk/dali/
Functional families
• Evolutionary relationships from strong structural similarities which are accompanied by functional or sequence similarities.
• Functional families are branches of the fold dendrogram where all pairs have a high average neural network prediction for being homologous.
Sequence families
• Representative subset of the Protein Data Bank extracted using a 25 % sequence identity threshold.
• All-against-all structure comparison was carried out within the set of representatives.
• Homologues are only shown aligned to their representative.
Compare 3D protein structures by Dali http://www.ebi.ac.uk/dali/
Fold types
• Fold types are defined as clusters of structural neighbors in fold space with average pairwise Z-scores (by Dali) above 2.
Structural neighbours of 1urnA (top left). 1mli (bottom right) has the same topology even though there are shifts in the relative orientation of secondary structure elements
Compare 3D protein structures by Dali http://www.ebi.ac.uk/dali/
Summary
Protein structure database (PDB)
Protein structure visualization software
Structural classification, databases and servers