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PDBsum entry 4boh
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Hydrolase/inhibitor
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PDB id
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4boh
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References listed in PDB file
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Key reference
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Title
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The tick-Derived anticoagulant madanin is processed by thrombin and factor xa.
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Authors
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A.C.Figueiredo,
D.De sanctis,
P.J.Pereira.
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Ref.
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Plos One, 2013,
8,
e71866.
[DOI no: ]
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PubMed id
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Abstract
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The cysteine-less peptidic anticoagulants madanin-1 and madanin-2 from the bush
tick Haemaphysalis longicornis are the founding members of the MEROPS inhibitor
family I53. It has been previously suggested that madanins exert their
functional activity by competing with physiological substrates for binding to
the positively charged exosite I (fibrinogen-binding exosite) of α-thrombin. We
hereby demonstrate that competitive inhibition of α-thrombin by madanin-1 or
madanin-2 involves binding to the enzyme's active site. Moreover, the blood
coagulation factors IIa and Xa are shown to hydrolyze both inhibitors at
different, although partially overlapping cleavage sites. Finally, the
three-dimensional structure of the complex formed between human α-thrombin and
a proteolytic fragment of madanin-1, determined by X-ray crystallography,
elucidates the molecular details of madanin-1 recognition and processing by the
proteinase. Taken together, the current findings establish the mechanism of
action of madanins, natural anticoagulants that behave as cleavable competitive
inhibitors of thrombin.
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