Thornton Group databases

1. Thornton Group databases Roman Laskowski, EBI Protein-Protein interaction server Protein-DNA interaction server DNA-binding protein structural families Scorecons http://www.ebi.ac.uk/Thornton/databases.html

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

3. Example PDBsum page

4. Protein page

5. Residue conservation

6. Protein page again

7. SAS hits for 1bpy

8. SAS annotations

9. SAS home page

10. DNA page

11. Ligand page

12. Enzyme reaction

13. Enzyme Structures Database

14. EC 1.1.1.1

15. PDBsum home again

16. Species page

17. PDBsum home again

18. Highlights page

19. Smallest structures page

20. 1tn1 page

21. Catalytic site atlas home page

22. CSA entry

23. CSA entry II

24. CSA partial search

25. MSA home page

26. MSA entry

27. Pita home page

28. Pita results for 1sip

29. Other databases Protein-Protein interaction server Protein-DNA interaction server DNA-binding protein structural families Scorecons Sidechain-sidechain interactions

30. ProFunc home page

31. SG structures of unknown function in the PDB Known function 350 (50.2%) Unknown function 347 (49.8%) Known function 350 (50.2%) Hypothetical 239 (34.3%) Others 108 (15.5%) Examples 697 SG structures in PDB as of Jul 2004 • 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

32. 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 I R 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 H P 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

33. Predicting function from 3D structure ALYFGHILVYSTFPNEEKALEIGRKLLEKRLIACFNAFEI RSGYWWKGEIVQDKEWAAIFKTTEEKEKELYEELRKLH PYETPAIFTLKVENILTEYNWLRESVLGS

34. ProFunc Fold and structural motifs n-residue templates Sequence scans Sequence search vs PDB Enzyme active sites SSM fold search Sequence search vs Uniprot Ligand binding sites Surface clefts Sequence motifs (PROSITE, BLOCKS, SMART, Pfam, etc) Residue conservation DNA binding sites DNA-binding HTH motifs Superfamily HMM library Reverse templates Nest analysis Gene neighbours

35. GARTfase Cholesterol oxidase IIAglc histidine kinase Template methods eg 189 enzyme active site templates … Carbamoylsarcosine amidohhydrase Ser-His-Asp catalytic triad Dihydrofolate reductase

36. Automatically generated templates 1. Small-molecule-binding templates 2. DNA-binding templates

37. “Reverse” templates (SiteSeer) 3-residue templates 1 2 3 4 5 6 7 8 9 … Query structure Query structure

38. Scoring template matches Ser Match to template: Arg Glu Template structure – 1mbb Query structure – 1hsk

39. Scoring template matches Ser Match to template: Arg Glu Template structure – 1mbb Query structure – 1hsk

40. Scoring template matches Ser Arg Glu Similar residues in neighbourhood: Template structure – 1mbb Query structure – 1hsk

41. Chitinase A Chitinase B 1ctn (538 a.a.) 1gpf (497 a.a.) An example:chitinase A and Bfrom S.marcescens Sequence identity of 28.7% (in 428 a.a. o/lap) So, function likely to be different

42. Template for E.C.3.2.1.14 comes from chitinase A structure 1ctn: Asp391 Glu315 Chitinase A Chitinase A is an enzyme (E.C.3.2.1.14) breaks chitin into its constituent GlcNac residues

43. 25 identical residues + 8 similar residues = = 50% local seq identity cf 28.7% overall Chitinase B matches E.C.3.2.1.14 template Chitinase B with a high site similarity score

44. Chitinase B is also an E.C.3.2.1.14 enzyme and breaks chitin into its constituent GlcNac residues Superposition of chitinase A and B