Membrane cofactor protein

CD45RO Known to be the isoform of leukosialin present on memory T cells CD46 Known to be z membrane cofactor protein... 

In photosynthesis, water oxidation is accomplished by photosystem II (PSII), which is a large membrane-bound protein complex (158-161). To the central core proteins D1 and D2 are attached different cofactors, including a redox-active tyro-syl residue, tyrosine Z (Yz) (158-162), which is associated with a tetranuclear manganese complex (163). These components constitute the water oxidizing complex (WOC), the site in which the oxidation of water to molecular oxygen occurs (159, 160, 164). The organization is schematically shown in Fig. 18. 

The Intention of this volume is to give a flavour of the types of problems in biochemistry that theoretical calculations can solve at present, and to illustrate the tremendous predictive power these approaches possess. With these aspects in mind, I have tried to gather some of the leading scientists in the field of theoretical/computational biochemistry and let them present their work. You will hence find a wide range of computational approaches, from classical MD and Monte Carlo methods, via semi-empirical and DFT approaches on isolated model systems, to Car-Parrinello QM-MD and novel hybrid QM/MM studies. The systems investigated also cover a broad range from membrane-bound proteins to various types of enzymatic reactions as well as inhibitor studies, cofactor properties, solvent effects, transcription and radiation damage to DNA. 

Biological cell membranes are multi-component systems consisting of a fluid bilayer lipid membrane (BLM) and integrated membrane proteins. The main structural features of the BLMs are determined by a wide variety of amphiphilic lipids whose polar head groups are exposed to water while hydrocarbon tails form the nonpolar interior. The BLMs act as the medium for biochemical vectorial membrane processes such as photosynthesis, respiration and active ion transport. However, they do not participate in the corresponding chemical reactions which occur in membrane-dissolved proteins and often need redox-active cofactors. BLMs were therefore mostly investigated by physical chemists who studied their thermodynamics and kinetic behaviour . ... 

Activated protein C in conjunction with its cofactor, protein S, plays a key role in the anticoagulant system by inactivating membrane-bound factors Va and Villa, The inability to inactivate procoagulant factors Va or Villa could disturb hemostasis, heighten the coagulation pathway, increase the generation of thrombin, and promote clot formation. In 1993 Dahlback reported familial thrombophilia caused by resistance to activated protein C (APC). In 1994... 

Cofactor proteins bind both the proteinase (enzyme) and the proenzyme (substrate). They bind to lipid membranes. 

The proteolytic reactions of the hemostatic system are neither catalytically efficient nor localized when proteinase and proteinase precursor only are present. The rapid, localized proenzyme activation required for normal hemostatic response occurs only in a complex of proteinase, proteinase precursor, and cofactor protein assembled on the surface of a damaged cell membrane, or in vitro, on the surface of phospholipid bilayers. The catalytic efficiency of an enzyme-catalyzed reaction is expressed by the ratio of the kinetic constants /ic and kJKm). In the activation complexes, kJKm values can be greater than lO M s . With proteinase and proenzyme alone, the kJKm values are only approximately 100 M s and thus the reactions are 10 times less efficient. Expressed in terms of the same amount of product formed in the two situations, a 10 increase represents the difference between requiring 1 minute and about 6 months to form the product ... 

It is helpful in the effort to understand activation complexes to consider complex formation, the reactions that occur in the complexes, and the demise of the complexes as proceeding in a sequence. First, a reversible, noncovalent association of proteinase, cofactor protein (strictly, activated cofactor protein), proteinase precursor, and membrane surface occurs to form the activation complex. This spontaneous association occurs as the result of complementary interaction sites on the protein molecules, e.g., the binding sites between proteinase and protein substrate, proteinase and cofactor protein, substrate and cofactor protein, and all three proteins with the membrane surface. Tissue factor normally exists as an integral membrane protein and is always associated with the membranes of cells in the vessel wall. The same processes are involved in the anticoagulant subsystem and, with a different surface, fibrin in the fibrinolytic system as well. 

The cofactor proteins (tissue factor. Factors V and VIII) serve as binding sites for other factors. Tissue factor is not related structurally to the other blood coagulation cofactors and is an integral membrane protein that does not require cleavage for active function. Factors V and VIII serve as procofactors, which, when activated by cleavage, function as binding sites for other factors. 

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