Thornton Group databasesRoman Laskowski, EBI

http://www.ebi.ac.uk/Thornton/databases.html

Protein-Proteininteraction server

Protein-DNAinteraction server

DNA-binding proteinstructural families

Scorecons

PDBsum: A database of the known 3D structures of proteins and nucleic acids

Example PDBsum page

Protein page

Residue conservation

Protein page again

SAS hits for 1bpy

SAS annotations

SAS home page

DNA page

Ligand page

Enzyme reaction

Enzyme Structures Database

EC 1.1.1.1

PDBsum home again

Species page

PDBsum home again

Highlights page

Smallest structures page

1tn1 page

Catalytic site atlas home page

CSA entry

CSA entry II

CSA partial search

MSA home page

MSA entry

Pita home page

Pita results for 1sip

Other databases

Protein-Protein interaction server

Protein-DNA interaction server

DNA-binding protein structural families

Scorecons

Sidechain-sidechain interactions

ProFunc home page

SG structures of unknown function in the PDB

Known function 350 (50.2%)

Unknown function 347 (49.8%)

697 SG structures in PDB as of Jul 2004

Known function 350 (50.2%)

Others108 (15.5%)

Hypothetical 239 (34.3%)

Examples• Hypothetical protein Af0491 from A. fulgidus• Ubiquitin-like domain from mouse• Signalling protein from sheep• Putative serine hydrolase from S.cerevisiae• Predicted glutamine amidotransferase from P. aeruginosa• Probable eukaryotic D-amino acid tRNA deacetylase• Molybdenum cofactor biosynthetic enzyme

Predicting function from 3D structure

A L Y F G H I L V Y S T F P N E E K A L E I G R K L L E K R L I A C F N A F E IR S G Y W W K G E I V Q D K E W A A I F K T T E E K E K E L Y E E L R K L HP Y E T P A I F T L K V E N I L T E Y N W L R E S V L G S

Predicting function from 3D structure

A L Y F G H I L V Y S T F P N E E K A L E I G R K L L E K R L I A C F N A F E IR S G Y W W K G E I V Q D K E W A A I F K T T E E K E K E L Y E E L R K L HP Y E T P A I F T L K V E N I L T E Y N W L R E S V L G S

Fold and structural motifs

SSM fold search

Surface clefts

Residueconservation

DNA-bindingHTH motifs

Nest analysis

Sequence motifs(PROSITE, BLOCKS,SMART, Pfam, etc)

Sequence scans

Sequence searchvs PDB

Sequence searchvs Uniprot

Superfamily HMMlibrary

Gene neighbours

n-residue templates

Enzyme active sites

Ligand binding sites

DNA binding sites

Reverse templates

ProFunc

GARTfaseCholesterol oxidaseIIAglc histidine kinase

Carbamoylsarcosineamidohhydrase

Dihydrofolate reductase Ser-His-Aspcatalytic triad

…

Template methodseg 189 enzyme active site templates

Automatically generated templates

1. Small-molecule-binding templates 2. DNA-binding templates

Query structureQuery structure

1 2 3

4 5 6

87 9

…

3-residue templates

“Reverse” templates (SiteSeer)

Template structure – 1mbb

Arg

Glu

Ser

Match to template:

Query structure – 1hsk

Scoring template matches

Template structure – 1mbb

Arg

Glu

Ser

Match to template:

Query structure – 1hsk

Scoring template matches

Template structure – 1mbb

Arg

Glu

Ser

Similar residues in neighbourhood:

Query structure – 1hsk

Scoring template matches

An example:chitinase A and B from S.marcescens

Sequence identity of 28.7% (in 428 a.a. o/lap)

So, function likely to be different

Chitinase A1ctn (538 a.a.)

Chitinase B1gpf (497 a.a.)

Chitinase A

Chitinase A is an enzyme (E.C.3.2.1.14)

breaks chitin into its constituent GlcNac residues

Template for E.C.3.2.1.14 comesfrom chitinase A structure 1ctn: Asp391

Glu315

Chitinase B Chitinase B matches E.C.3.2.1.14 template

with a high site similarity score

25 identical residues+ 8 similar residues

= 50% local seq identitycf 28.7% overall=

Superposition of chitinase A and B

Chitinase B is also an E.C.3.2.1.14 enzyme and breaks chitin into its constituent GlcNac residues