a brief introduction to protein structure and x-ray crystallography
TRANSCRIPT
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Protein
Structure& FunctionTeh Aik Hong
Centre for Chemical Biology (CCB@USM)
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Why structure?
Why structure?
Why structure?
Why structure?
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Mecha-
nism
To understand how proteins function how
they transport oxygen, detect light, synthesize
or break down other molecules, etc.
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Mecha-
nism
Modifi-cation
To engineer a protein in order to improve or
alter its activity, thermostability, etc.
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Mecha-
nism
Modifi-cation
DrugDesign
To design drugs that can inhibit
proteins from harmful organisms,
cancel cells, etc.
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Myoglobin solved by John Kendrew in 1956
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Myoglobin in 1959 Myoglobin in detail
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Hemoglobin in action
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A single mutation (E6V) causes sickle-cell disease
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Photo 51 taken by Rosalind Franklin in 1952
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DNA structure discovered in 1952
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X-RayCrystallo-
graphy
NMRElectron
Microscopy
StructurePrediction
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Taken byRntgen
in 1896
Soft tissue
Gold ring
Diamond?
Bone
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Cloning
Expression & Purification
Crystallization
Data Collection
Structure Determination
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Cloning
Expression & Purification
Crystallization
Data Collection
Structure Determination
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Cloning
Expression & Purification
Crystallization
Data Collection
Structure Determination
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Cloning
Expression & Purification
Crystallization
Data Collection
Structure Determination
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Cloning
Expression & Purification
Crystallization
Data Collection
Structure Determination
N2stream
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Cloning
Expression & Purification
Crystallization
Data Collection
Structure Determination
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Crystallization is like a box of chocolates;
you never know what you're gonna get.
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InitialScreening
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Optimization
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Beauty is only skin deep.
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Goodcrystals?
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A thermostable -amylase
Ca2+
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Hemoglobin HGbI with high O2affinity
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Unique hemoglobin HGbIV involved in signalling
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Open Closed
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Conformational shift between the two forms
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Thank You