Identification of critical molecular interactions mediating heparin activation of antithrombin: Implications for the design of improved heparin anticoagulants

Trends in Cardiovascular Medicine

Volumn 12, Issue 5, 2002, Pages 198-205

  Olson, Steven T ^a,b   Björk, Ingemar ^a   Bock, Susan C ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICOAGULANT AGENT; ANTITHROMBIN; HEPARIN; PENTASACCHARIDE; TRISACCHARIDE; ARGININE; LYSINE;

AMINO ACID SUBSTITUTION; BINDING AFFINITY; BINDING SITE; BLOOD CLOTTING; CONFORMATIONAL TRANSITION; ENZYME ACTIVATION; HUMAN; MUTAGENESIS; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN PROTEIN INTERACTION; REVIEW; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; METABOLISM; PROTEIN BINDING; STRUCTURE ACTIVITY RELATION;

ANTICOAGULANTS; ANTITHROMBINS; ARGININE; DRUG DESIGN; HEPARIN; HUMAN; LYSINE; MODELS, MOLECULAR; PROTEIN BINDING; STRUCTURE-ACTIVITY RELATIONSHIP; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S.; HUMANS;

EID: 0036021104     PISSN: 10501738     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1050-1738(02)00160-3     Document Type: Review

References (40)

1. The role of Arg46 and Arg47 of antithrombin in heparin binding
2. Lysine 114 of antithrombin is of crucial importance for the affinity and kinetics of heparin pentasaccharide binding
3. The region of antithrombin interacting with full-length heparin chains outside the high-affinity pentasaccharide sequence extends to Lys 136 but not to Lys 139
4. Insight into residues critical for antithrombin function from an expanded database that includes sequences of frog, turtle, and ostrich antithrombin
5. Low molecular weight heparins
6. Antithrombin. A bloody important serpin
7. The pH dependence of serpin-proteinase complex dissociation reveals a mechanism of complex stabilization involving inactive and active conformational states of the proteinase which are perturbable by calcium
8. Structure-activity relationship in heparin; a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity
9. Heparin enhances the specificity of antithrombin for thrombin and factor Xa independent of the reactive center loop sequence. Evidence for an exosite determinant of factor Xa specificity in heparin-activated antithrombin
10. Role of ternary complexes, in which heparin binds both antithrombin and proteinase, in the acceleration of the reactions between antithrombin and thrombin or factor Xa
11. Localization of anticoagulantly active heparan sulfate proteoglycans in vascular endothelium; antithrombin binding on cultured endothelial cells and perfused rat aorta
12. Mechanism of heparin activation of antithrombin. Role of individual residues of the pentasaccharide activating sequence in the recognition of native and activated states of antithrombin
13. Mechanism of heparin activation of antithrombin; evidence for an induced-fit model of allosteric activation involving two interaction subsites
14. Role of Arg 129 in heparin binding and activation of antithrombin
15. Rational design of synthetic heparin analogues with tailor-made coagulation factor inhibitory activity
16. The conformational activation of antithrombin
17. Mechanism of heparin activation of antithrombin. Evidence for reactive center loop preinsertion with expulsion upon heparin binding
18. Structure of a serpin-protease complex shows inhibition by deformation
19. Complete antithrombin deficiency in mice results in embryonic lethality
20. The anticoagulant activation of antithrombin by heparin
21. Partitioning of serpin-proteinase reactions between stable inhibition and substrate cleavage is regulated by the rate of serpin reactive center loop insertion into β-sheet A
22. Cloned bovine aortic endothelial cells synthesize anticoagulantly active heparin sulfate proteoglycan
23. Role of arginine 132 and lysine 133 in heparin binding to and activation of antithrombin
24. Mechanism of action of heparin and heparin-like antithrombotics
25. Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement
26. Binding of high affinity heparin to antithrombin III. Stopped flow kinetic studies of the binding interaction
27. Synthesis of thrombin-inhibiting heparin mimetics without side effects
28. Calcium enhances heparin catalysis of the antithrombin-factor Xa reaction by a template mechanism; evidence that calcium alleviates Gla domain antagonism of heparin binding to factor Xa
29. The importance of lysine 125 for heparin binding and activation of antithrombin
30. Rapid, electrostatically assisted association of proteins
31. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins
32. The 2.6 Å structure of antithrombin indicates a conformational change at the heparin binding site
33. Formation of the covalent serpin-proteinase complex involves translocation of the proteinase by more than 70 Å and full insertion of the reactive center loop into β-sheet A
34. Further characterization of the antithrombin-binding sequence in heparin
35. The oligosaccharide side chain on Asn-135 of α-antithrombin, absent in β-antithrombin, decreases the heparin affinity of the inhibitor by affecting the heparin-induced conformational change
36. A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement
37. A mechanism for heparin-induced potentiation of antithrombin III
38. Antithrombin and its inherited deficiency states
39. Facilitated target location in biological systems