Binding and release

The most striking feature of transferrin chemistry is that iron is bound with extraordinary avidity, yet it can be released without any denaturation and the protein can be recycled through many cycles of uptake and release. The mechanisms by which this is done are of fundamental importance to understanding biological transport processes. 

In vivo uptake of iron by transferrins usually involves its addition as a ferric-chelate complex, to prevent hydrolytic attack on the ferric ion (211). Complexes such as ferric citrate and ferric nitrilotriacetate are commonly used. Under these conditions, kinetic schemes for the uptake of iron by transferrins have identified five steps in the formation of the specific metal-anion-transferrin ternary complex (120). These may be summarized as follows. 

Detachment of one or more ligands from the added metal chelate. 

Formation of a quaternary transferrin-anion-metal-chelate complex. 

Conformational change to the final specific transferrin complex. 

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AH of the reactions considered to be useful in the production of hemoglobin-based blood substitutes use chemical modification at one or more of the sites discussed above. Table 2 Hsts the different types of hemoglobin modifications with examples of the most common reactions for each. Differences in the reactions are determined by the dimensions and reactivity of the cross-linking reagents. Because the function of hemoglobin in binding and releasing... 

The loop region between the two a helices binds the calcium atom. Carboxyl side chains from Asp and Glu, main-chain C =0 and H2O form the ligands to the metal atom (see Figure 2.13b). Thus both the specific main-chain conformation of the loop and specific side chains are required to provide the function of this motif. The helix-loop-helix motif provides a scaffold that holds the calcium ligands in the proper position to bind and release calcium. 

The GroEL-GroES complex binds and releases newly synthesized polypeptides in an ATP-dependent cycle... 

Fenton, W.A., et al. Residues in chaperonin GroEL required for polypeptide binding and release. 

The steady-state balance of the Ca pump and plasma membrane leaks of Ca determines the resting intracellular free Ca concentration. Kinetically, all the other membrane bound compartments and their transport processes are analogous to buffer systems with various rates of binding and release. The essential point is that all the other pools must come to steady-state with the intracellular free concentration. Thus, the plasma membrane Ca -pump for the Ca economy of the cell has primacy. 

Flynn, G.C., Chappell, T.G., Rothman, J.E. (1989). Peptide binding and release by proteins implicated as catalysts of protein assembly. Science 245, 385-390. 

Fig. 3 Binding and release of tropoelastin. The elastin receptor consists of a 67 kDa peripheral subunit (EBP) with two transmembrane proteins of 61 and 55 kDa. The 67 kDa protein binds tropoelastin and galactosugars through two separate sites, (a) Tropoelastin binds to the intact EBP complex, (b) Upon binding of a galactosugar, the EBP loses its affinity for both tropoelastin and the membrane-bound protein, which leads to the release of tropoelastin. Reproduced from [8] with permission from John Wiley and Sons, copyright 1998...

Cycles of binding and release of the protein to the chaperone result in pulling of its polypeptide chain through the membrane. 

The binding and release of oxygen by hemoglobin can be represented as a ligand-exchange equilibrium at the sixth coordination site on the Fe ion. Each of the four polypeptide chains of hemoglobin contains one heme unit, so... 

ATP certainly fulfils the criteria for a NT. It is mostly synthesised by mitochondrial oxidative phosphorylation using glucose taken up by the nerve terminal. Much of that ATP is, of course, required to help maintain Na+/K+ ATPase activity and the resting membrane potential as well as a Ca +ATPase, protein kinases and the vesicular binding and release of various NTs. But that leaves some for release as a NT. This has been shown in many peripheral tissues and organs with sympathetic and parasympathetic innervation as well as in brain slices, synaptosomes and from in vivo studies with microdialysis and the cortical cup. There is also evidence that in sympathetically innervated tissue some extracellular ATP originates from the activated postsynaptic cell. While most of the released ATP comes from vesicles containing other NTs, some... 

The complex Ni[(S2C2(CF3)2)]2 (392) is able to bind light olefins selectively and reversibly.1081 According to Scheme 4, the reaction of olefins with (392) can be controlled electrochemically, where the oxidation state-dependent binding and release of olefins is fast on the electrochemical timescale. Olefin binding is supposed to occur via the ligand S-donors. 

Metallothioneins (MT) are unique 7-kDa proteins containing 20 cysteine molecules bounded to seven zinc atoms, which form two clusters with bridging or terminal cysteine thiolates. A main function of MT is to serve as a source for the distribution of zinc in cells, and this function is connected with the MT redox activity, which is responsible for the regulation of binding and release of zinc. It has been shown that the release of zinc is stimulated by MT oxidation in the reaction with glutathione disulfide or other biological disulfides [334]. MT redox properties led to a suggestion that MT may possesses antioxidant activity. The mechanism of MT antioxidant activity is of a special interest in connection with the possible antioxidant effects of zinc. (Zinc can be substituted in MT by some other metals such as copper or cadmium, but Ca MT and Cu MT exhibit manly prooxidant activity.)... 

Detailed three-dimensional models of P-gp-substrate complexes representing the various steps of the catalytic cycle would be significantly helpful in elucidating the molecular mechanism for substrate binding and release. The relatively poor 3D structural information available [14—16] and the complex mechanism for compounds undergoing P-gp-compound interactions explain why only a few groups have attempted to build and study 3D homology models for P-gp [56,58,60,70]. 

Robertson DHL, Marie AD, Veggerby C, Hurst JL, Beynon RJ (2001) Characteristics of ligand binding and release by major urinary proteins. In Marchlewska-Koj A, Lepri JJ, Muller-Schwarze D (eds) Chemical signals invertebrates IX. Cluver/Plenum, New York, p 169... 

Teng L, Crooks PA, Dwoskin LP. (1998). Lobeline displaces [3H]dihydrotetrabenazine binding and releases [3H]dopamine from rat striatal synaptic vesicles with d-amphetamine. J Neurochem. 71(1) 258-65. 

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