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PDBemotif
A web based integrated search service to
understand ligand binding and secondary
structure properties in macromolecular
structures
EBI is an Outstation of the European Molecular Biology Laboratory.
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
Comparing two ligand binding sites
What is the environment around alpha-D-mannose and beta-D-mannose?
Query based on binding environment
What binds ASP ASP HIS LYS ?
PDBesite-interaction between a ligand and a residue
How does ATP generally interact with LYS in all structures ?
The PDBe-motif Search Interface
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 (Ligandaminoacid, 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
Starting a Search
Using Sucrose Specific porin as an example to explore the site
Results
• Sequences
• 3Dmotif
• Ligand
environment
• Ligand bonds
1.
2.
3.
4.
Secondary Structure pattern
aa sequence
Ligand binding
Searching further based on
Secondary structures
1a0t
3D-Motifs:
Motif information for each chain and bound ligands presented individually
Search Results for 1a0t –based on 3D motif
configuration(195:IHWI,196:HWID)
• Predominant
secondary
structure
element –
beta sheets
Something Interesting!!!!
1a0t
1ofm
• Predominantly beta sheet but tertiary structure quite
different
• Both cases the 3D motif is engaged in interacting with
hexose sugar moieties
• Significance in structure-function relationships
Ligand Binding Environment
• Residues are colour
coded based on their
nature of interactions
with the ligand
• Provides detailed
3dimensional
information about the
ligand binding
environment
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 environmentfacilitating the transport
Calcium Binding
Lots of negatively charged amino acids
What type of PROSITE pattern is involved in
binding a 4Fe-4S cluster?
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
How does GTP interact with LYS?
Statistics -Binding Interactions GTP vs Lys
Colour coded based on nature
of interactions
Combining Different Search Items
Pattern search
Search for Small Molecule
Combining both the queries
Multiple 3D Alignment of GXXXXGKT motif/Walker A motif
Particular amino
acid sequence
giving rise
to secondary
structure pattern –
defining role in
cellular processes
PDBe-Site – Another Useful Tool to Analyse Ligand Environment
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 !!
PDBesite Results Page
Some uses of the data obtained from PDBesite analysis:
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•
•
Compare ligand environments.
Analyze interactions between
ligand and protein.
Compare binding environment.
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•
•
Look for ligands within a
certain environment.
Superpose binding sites and
ligands.
Predict what could bind that
empty pocket in your
structure