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PDBsum entry 4lz4
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Hydrolase/hydrolase inhibitor/DNA
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PDB id
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4lz4
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References listed in PDB file
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Key reference
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Title
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Dissecting the contribution of thrombin exosite i in the recognition of thrombin binding aptamer.
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Authors
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A.Pica,
I.Russo krauss,
A.Merlino,
S.Nagatoishi,
N.Sugimoto,
F.Sica.
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Ref.
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Febs J, 2013,
280,
6581-6588.
[DOI no: ]
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PubMed id
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Abstract
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Thrombin plays a pivotal role in the coagulation cascade; therefore, it
represents a primary target in the treatment of several blood diseases. The
15-mer DNA oligonucleotide 5'-GGTTGGTGTGGTTGG-3', known as thrombin binding
aptamer (TBA), is a highly potent inhibitor of the enzyme. TBA folds as an
antiparallel chair-like G-quadruplex structure, with two G-tetrads surrounded by
two TT loops on one side and a TGT loop on the opposite side. Previous
crystallographic studies have shown that TBA binds thrombin exosite I by its TT
loops, T3T4 and T12T13. In order to get a better understanding of the
thrombin-TBA interaction, we have undertaken a crystallographic characterization
of the complexes between thrombin and two TBA mutants, TBAΔT3 and TBAΔT12,
which lack the nucleobase of T3 and T12, respectively. The structural details of
the two complexes show that exosite I is actually split into two regions, which
contribute differently to TBA recognition. These results provide the basis for a
more rational design of new aptamers with improved therapeutic action.
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