|
Deletion of amino acid
residues 33-46 in growth hormone alters the
hydrophobicity of the molecule
Amtul Jamil Sami
Institute
of Biochemistry and Biotechnology, University of the Punjab,
Lahore, Pakistan. E-mail:
amtuljamilsami@yahoo.com.
Accepted 22
December, 2009 |
|
Growth
hormone
(GH)
variants
have
been
studied
for
the
structure-function
relationship
of
the
molecule.
The
presence
of
a potential
alternate
splicing
point
in mRNA
in bGH
gene
at exon
3, similar
to hGH
has
been
reported
by
workers.
Early
investigation
on
the
characteristics
of
the chemistry
of
20k oGH
showed
that
the
molecule
was
produced
by
site-directed
mutagenesis
by
deleting
amino
acid
residues
33-46
and
the
resultant
DNA
was expressed
in
E.
coli
under
the
control
of
lac promoter
in pUC
based
plasmid.
The
mutant
protein
remained
insoluble
and
did
not
refold.
To
investigate
the
effect
of
deletion
on
the chemistry
of
the
molecule,
computational
biology
tools
were
employed.
The
mutant
with
the
deletion
of
amino
acid
residues
33-46,
was
designed
and
the
model
was
visualized
on
computer.
The
structure
of
20k
bGH
was
compared
with
bGH
and
dissected
for
hydrogen
bonds and
hydro-phobicity.
Computational
biology
tools
were
helpful
in elucidating
the
role
of
33-46
amino
acid
residues
domain in
the
chemistry
of
the molecule.
Furthermore,
it
was
revealed
that
removal
of
amino
acid
residues
33-46
which
formed
the
hydrogen bonds involving
Glu
33,
Gln 46,
Pro 38,
Arg
42,
Tyr
43,Ala
51,
Thr
48,
Asn 47,
led
to
the
formation
of
new
hydrogen bonds between
Thr
33,
Tyr
144,
Asn
32,
Asn
32 and
Ser
and
Asp
153. The
removal
of
the
amino
acids
33-46
decreased
the
hydro-phobicity
of
the
first
helix
of
bGH
molecule,
as compared
to
20k
hGH,
thus
altering
the
solubility
of
the
molecule,
confirming
the
earlier
reported
results
for
ovine
growth
hormone
with
same
deletion.
Key
words:
Ovine growth hormone, 20k hGH, hydro-phobicity. |
