Blood coagulation structure

Similarly to blood coagulation, reactions of fibrinolysis occur on the interface of fluid-and solid-phase structures, generally in transiently formed compartments. 

M6. Moller, L. B., Structure and function of urokinase receptor. Blood Coagulation Fibrinolysis 4, 293-303 (1993). 

Platelet. Disc-like structure, 2-4 mm in diameter, found in the blood of all mammals and chiefly known for its role in blood coagulation. 

Vlasuk GP. Structural and functional characterization of tick anticoagulant peptide (TAP) a potent and selective inhibitor of blood coagulation factor Xa. Thrombosis and Haemostasis 1993 70 212-216. 

In ihe mammalian body, calcium is required to insure the integrity and permeability of cell membranes. 10 regulate nerve and muscle excitubiliiy. to help maintain normal muscular contraction, and to assure cardiac rhvthmicity. Calcium plays an essential role in several of ihe enzymatic steps involved in blood coagulation and also activates certain other enzyme-catalyzed reactions not involved in any of ihe foregoing processes. Calcium is ihe niosi important element of bone sail. Together with phosphate and carbonate, calcium confers on bone most of its mechanical and structural properties. 

I 14 Kane WH, Davie EW. Blood coagulation factors V and VIII structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders. Blood 1988 71 539-555. 

Muszbeck L, Adany R, Mikkola H. Novel aspects of blood coagulation Factor XIII. Structure, distribution, activation and function. Crit Rev Clin Lab Sci 1996 33 357-421. 

Heparin acts by binding to anti thrombin III, which serves as a major inhibitor of serine protease clotting enzymes. Abruptly ending heparin treatment can be hazardous because of reduced levels of antithrombin III. Coumarins, typified by warfarin, are structurally similar to vitamin K, which plays an important role in blood coagulation. By interfering with the function of vitamin K, vitamin K-dependent proteins such as clotting factors VII, IX, X and prothrombin are reduced. 

Changes in the interaction type of Gin side chains can also occur without major spatial reorientations, as shown by a comparison of the blood coagulation factor Xa structures lfax and lxkb. In lfax, the Ne2 atom of Glnl92 forms an H-bond with the carboxylate group of the ligand. Conversely, in lxkb the face of the amide plane forms a Jt-s lacking interaction with one aromatic ring of the biphenyl moiety. 

Structure analysis of several proteases involved in blood coagulation and fibrinolysis reveals a diverse, sometimes repetitive, assembly of discrete protein modules (Fig. 9.4) [56]. While these modules represent independent structural units with individual folding pathways, their concerted action contributes to function and specificity in the final protein product. On the genetic level, these individual modules are encoded in separate exons. Over the course of modular protein evolution, new genes are created by duplication, deletion, and rearrangement of these exons. Mechanistically, the exon shuffling actually takes place in the intervening intron sequences (intronic recombination - for further details see [10]). 

Banner, D. W., D Arcy, A. D., Chene, C., Winkler, F. K., Guha, A., Konigsberg, W. H., Nermerson, Y, and Kirchhofer, D. (1996). The crystal structure of the complex of blood coagulation factor Vila with soluble tissue factor. Nature 380, 41-46. 

T. Iwama, S.-H. Kim, Structural basis for chemical inhibition of human blood coagulation factor Xa, Proc. Natl. Acad. Sci. U. S. A. 1998, 6630-6635. 

Davie, E.W., Ichinose, A., and Leytus, S.P. (1986). Structural features of the proteins participating in blood coagulation and fibrinolysis. Cold Spring Harbor Symposia on Quantitative Biology LI, 509 514. 

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