Structural Genomics
Dr. Fazli Wahid
COMSATS Institute of Information Technology, Abbottabad
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Structural Genomics
Related to the discipline of proteomics is that of structural
genomics.
The latter focuses upon the large-scale systematic study of gene
product structure.
The basic approach to structural genomics entails the cloning and
recombinant expression of cellular proteins, followed by their
purification and three-dimensional structural analysis.
High-resolution determination of a protein’s structure is amongst
the most challenging of molecular investigations.
By the year 2000, protein structure databanks housed in the region
of 12,000 entries.
However, such databanks are highly redundant, often containing
multiple entries describing variants of the same molecule.
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Structural Genomics
For example, in excess of 50 different structures of ‘insulin’ have
been deposited (e.g. both native and mutated/engineered forms
from various species, as well as insulins in various polymeric forms
and in the presence of various stabilizers and other chemicals).
In reality, by the year 2000, the three-dimensional structure of
approximately 2000 truly different proteins had been resolved.
Until quite recently, X-ray crystallography was the technique used
almost exclusively to resolve the three-dimensional structure of
proteins.
As well as itself being technically challenging, a major limitation
of X-ray crystallography is the requirement for the target protein to
be in crystalline form.
It has thus far proven difficult/impossible to induce the majority
of proteins to crystallize.
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Structural Genomics
NMR is an analytical technique that can also be used to determine
the three-dimensional structure of a molecule, and without the
necessity for crystallization.
For many years, even the most powerful NMR machines could
resolve the three-dimensional structure of only relatively small
proteins (less than 20–25 kDa).
However, recent analytical advances now render it possible to
analyse much larger proteins by this technique successfully.
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Structural Genomics
NMR is an analytical technique that can also be used to determine
the three-dimensional structure of a molecule, and without the
necessity for crystallization.
For many years, even the most powerful NMR machines could
resolve the three-dimensional structure of only relatively small
proteins (less than 20–25 kDa).
However, recent analytical advances now render it possible to
analyse much larger proteins by this technique successfully.
The ultimate goal of structural genomics is to provide a complete
three-dimensional description of any gene product.
Also, as the structures of more and more proteins of known
function are elucidated, it should become increasingly possible to
link specific functional attributes to specific structural attributes.
As such, it may prove ultimately feasible to predict protein
function if its structure is known, and vice versa.
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COMSATS Institute of Information Technology, Abbottabad
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