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allied
academies
J Pharmacol Ther Res 2017 Volume 1 Issue 2
November 02-03, 2017 Chicago, USA
4
th
International Congress on
International Conference and Exhibition on
Drug Discovery, Designing and Development
Biochemistry, Molecular Biology: R&D
&
S
ilicateins play the major role in formation of silica skeletal
structures in marine sponges. They are members of the
cathepsin family of cysteine proteases with 65% homology
with human
Cathepsin L.
The critical substitution that turns
proteolytic activity to silica polymerization is supposed to
be Cys to Ser substitution in the catalytic triad (Cys-His-
Asn). We synthesized a novel silica precursor for silicateins
– tetrakis(glycerol)orthosilicate (TGS). We have tested TGS
as a substrate for silicatein A1 from the marine sponge
Latrunculia oparinae. It effectively formed silica particles
with and the amount of polymerized silica 1000-fold greater
than previously described for silicatein alpha S.domuncula
and tetraethyl orthosilicate. Then we investigated the activity
of few silicatein point mutants – we substituted catalytic Ser
and its flanking residues to the residues from its cathepsin
homolog (S25C, Y26W, GAS23-25KSC). All the proteins retain
silicatein activity. Alaninemutants of the catalytic triad (S25A,
H163A, or N187A) still have silicatein activity. We hyposized
that mechanismof silicatein enzymatic activity involves some
other features of the protein and checked human cathepsin
L for the presence of silicatein activity. And found that it is
also capable to polymerise silica from TGS. So, new more
available precursor allowed us to find new enzymatic activity
of human cathepsin L and showed that our understanding of
silicatein activity mechanism call for reevaluation.
e:
povarovanv@gmail.comAn unexpected tolerance of silicatein activity to mutations revealed due to a novel water-soluble silica
precursor
Natalia V. Povarova
1
, Nikolay A. Barinov
2
, Nadezda M. Markina
1
, Mikhail S. Baranov
1
, Valery B. Kozhemyako
3
and
Konstantin A. Lukyanov
1
1
Institute of bioorganic chemistry, Russia
2
Federal Research and Clinical Center of Physical-Chemical Medicine, Russia
3
Pacific Institute of Bioorganic Chemistry, Russia