1 / 31

Sanchayita Sen, Ph.D. PDB Depositions

PDBemotif – A web based integrated search service to understand ligand binding and secondary structure properties in macromolecular structures. Sanchayita Sen, Ph.D. PDB Depositions. PDBe-motif ( http://www.ebi.ac.uk/pdbe-site/PDBeMotif ).

micheal
Download Presentation

Sanchayita Sen, Ph.D. PDB Depositions

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PDBemotif – A web based integrated search service to understand ligand binding and secondary structure properties in macromolecular structures Sanchayita Sen, Ph.D. PDB Depositions

  2. PDBe-motif (http://www.ebi.ac.uk/pdbe-site/PDBeMotif) • Integrated search system for protein and nucleic acid structures. • User can construct a query based on - a) Ligands and their 3D environment b) protein families (SCOP, CATH, UNIPROT, EC-number) c) protein secondary structures and different 3D motifs (PROSITE, beta turn, catalytic sites etc.) d) protein Φ/Ψ angle sequences • Results - a) Sequence multiple alignment b) 3D multiple alignment of fragments, motifs and protein chains. c) Interactions statistics d) Motifs characteristics and properties distribution charts. 2 31.10.07

  3. The PDBe-motif Search Interface

  4. Different Search Options - • PDB Header Search – PDB ID, Experiment Type, author name …. • Molecule Binding – Ligand 3-letter code, metal site geometry – looking for covalent, H-bonds, Van der Waals, planar interactions – distribution against amino acids, nucleic acids, ligands, Prosite motifs etc. • Pair bonds – interactions statistics between a pair of residues (Ligand-aminoacid, ligand-ligand, ligand-nucleic acid etc.) • Motif binding – search for sequence pattern –distribute against ligands, secondary structures, 3D motifs • Search – combine different sources of data generate your query • Upload your own PDB file for analysis

  5. Starting a Search Using Sucrose Specific porin as an example to explore the site

  6. Sequences 3Dmotif Ligand environment Ligand bonds Results

  7. Secondary Structure pattern aa sequence Ligand binding Searching further based on Secondary structures

  8. 1a0t

  9. 3D-Motifs: Motif information for each chain and bound ligands presented individually

  10. Search Results for 1a0t –based on 3D motif configuration(195:IHWI,196:HWID) Predominant secondary structure element – beta sheets

  11. Predominantly beta sheet but tertiary structure quite different Something Interesting!!!! 1a0t 1ofm

  12. Both cases the 3D motif is engaged in interacting with hexose sugar moieties Significance in structure-function relationships

  13. Residues are colour coded based on their nature of interactions with the ligand Provides detailed 3dimensional information about the ligand binding environment Ligand Binding Environment

  14. Sucrose Binding • Aromatic amino acid sidechains (Tyr, Phe) are parallel to hexose/pentose sugar ring – helps in gliding mechanism • Lots of charged amino acids in the environment-facilitating the transport

  15. Calcium Binding Lots of negatively charged amino acids

  16. What type of PROSITE pattern is involved in binding a 4Fe-4S cluster?

  17. Interaction Statistics • Clicking on each bar returns a list of PDB entries • The bars are proportionally colour coded based on the nature of interactions between the ligand and motif

  18. How does GTP interact with LYS?

  19. Statistics -Binding Interactions GTP vs Lys Colour coded based on nature of interactions

  20. Combining Different Search Items

  21. Pattern search

  22. Search for Small Molecule

  23. Combining both the queries

  24. Multiple 3D Alignment of GXXXXGKT motif/Walker A motif Particular amino acid sequence giving rise to secondary structure pattern – defining role in cellular processes

  25. PDBe-Site – Another Useful Tool to Analyse Ligand Environment

  26. Search options in the PDBe-site page • Define search by ligand • Define search by sequence motif (pattern) • Define search by metal site geometry • Define search by environment • has same environment • has similar environment Upload your own PDB file for analysis !! 27 31.10.07 Macromolecular Structure Database

  27. Compare ligand environments. Analyze interactions between ligand and protein. Compare binding environment. Look for ligands within a certain environment. Superpose binding sites and ligands. Predict what could bind that empty pocket in your structure PDBesite Results Page Some uses of the data obtained from MSDsite analysis:

  28. Comparing two ligand binding sites What is the environment aroundalpha-D-mannoseandbeta-D-mannose? 29 31.10.07 http://www.ebi.ac.uk/msd

  29. MSDsite query based on binding environment What binds ASP ASP HIS LYS ? 30 31.10.07 Macromolecular Structure Database

  30. MSDsite-interaction between a ligand and a residue How does ATP generally interact with LYS in all structures ? 31 31.10.07 http://www.ebi.ac.uk/msd

More Related