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PDBsum entry 1l4z
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Hydrolase/blood clotting
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PDB id
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1l4z
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Effects of deletion of streptokinase residues 48-59 on plasminogen activation.
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Authors
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N.Wakeham,
S.Terzyan,
P.Zhai,
J.A.Loy,
J.Tang,
X.C.Zhang.
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Ref.
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Protein Eng, 2002,
15,
753-761.
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PubMed id
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Abstract
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Streptokinase (SK) is a thrombolytic agent widely used for the clinical
treatment of clotting disorders such as heart attack. The treatment is based on
the ability of SK to bind plasminogen (Pg) or plasmin (Pm), forming complexes
that proteolytically activate other Pg molecules to Pm, which carries out
fibrinolysis. SK contains three major domains. The N-terminal domain, SKalpha,
provides the complex with substrate recognition towards Pg. SKalpha contains a
unique mobile loop, residues 45-70, absent in the corresponding domains of other
bacterial Pg activators. To study the roles of this loop, we deleted 12 residues
in this loop in both full-length SK and the SKalpha fragment. Kinetic data
indicate that this loop participates in the recognition of substrate Pg, but
does not function in the active site formation in the activator complex. Two
crystal structures of the deletion mutant of SKalpha (SKalpha(delta)) complexed
with the protease domain of Pg were determined. While the structure of
SKalpha(delta) is essentially the same as this domain in full-length SK, the
mode of SK-Pg interaction was however different from a previously observed
structure. Even though mutagenesis studies indicated that the current complex
represents a minor interacting form in solution, the binding to SKalpha(delta)
triggered similar conformational changes in the Pg active site in both crystal
forms.
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