Allosteric activation of human α-thrombin through exosite 2 by suramin analogs
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Graphical abstract
Highlights
► Suramin binds to thrombin through exosite 2. ► Suramin activates thrombin at low micromolar range. ► At higher suramin concentration thrombin is inhibited. ► A series of suramin analogs reveals the mechanism for activation and inhibition.
Abbreviations used
FPRCK
D-Phe-Pro-Arg-chloromethylketone
Suramin
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino-3,1-(4-methylphenylene)carbonylimino]]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
NF037
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino-3,1-phenylenecarbonylimino]]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
NF127
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino-3,1-(4-ethylphenylene)carbonylimino]]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
NF151
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino-3,1-(4-isopropylphenylene)carbonylimino]]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
NF198
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino-3,1-(4-phenylphenylene)carbonylimino]]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
NF157
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino-3,1-(4-fluorophenylene)carbonylimino]]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
NF258
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino-3,1-(4-chlorophenylene)carbonylimino]]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
NF260
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino-3,1-(4-(methoxyphenylene) carbonylimino]]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
NF222
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino-3,1-(4-(methoxymethyl)phenylene)carbonylimino]]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
NF023
8,8′-[carbonylbis[imino-3,1-phenylenecarbonylimino]bis[naphthalene-1,3,5-trisulfonic acid] hexasodium salt
MK012
4,4′-[carbonylbis[imino-3,1-phenylenecarbonylimino]]bis[benzene-1,3-disulfonic acid] tetrasodium salt
S-2238
H–D-Phe-Pip-Arg-p-nitroanilide
TBS
20 mM Tris–HCl, 150 mM NaCl, pH 7.5
Keywords
Thrombin
Fibrinogen
Suramin
Exosite-2
Allosteric activation
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These authors contributed equally to this work.
Copyright © 2012 Elsevier Inc.