Binding Site Localization

Figure 1.8 Drug binding site localization data in P-gp. Residues (in green, red, and yellow) thatare interpreted as contributing to drug binding in P-gp (see Table 1.1 and text) are mapped onto...

Bidard, J., et al. (1989). Analogies and Differences in the Mode of Action and Properties of Binding Sites (Localization and Mutual Interactions) of Two K+ Channel Toxins, MCD Peptide and Dendrotoxin I, Brain Res. 495 45-57. 

Fig. 9 Guan s supramolecular triblock copolymers with binding sites localized within soft, microphase-segregated domains, (a) Molecular structure and cartoon of the polymer morphology, (b) Self-healing of a triblock after cutting and healing at 45 °C. Adopted with permission from [63]. Copyright 2012 John Wiley Sons, Inc.

The plasminogen molecule contains several sites that specifically bind a number of antifibrinolytic amino acids, such as lysine [56-87-1] and S-aminocaproic acid [60-32-2] (EACA). These sites are known as lysine binding sites (LBS), and are localized mainly to the A or heavy chain of the molecule. One is located in K4 and at least one more is in K1 through K3. One LBS, which is beheved to reside in Kl, has a stronger affinity for EACA, whereas the others have a weaker affinity. The LBS are important for the interaction of plasminogen with several components of the endogenous fibrinolytic system. 

The central 10 base pairs of the palindromic DNA molecule have a regular B-DNA structure. Between base pairs 5 and 6 in each half of the fragment (base pairs are counted from the center) there is a 40° kink which causes these base pairs to be unstacked (Figure 8.24a). After this localized kink the two end regions have an essentially B-DNA structure. The kink occurs at a TG step in the sequence GTG. These TG steps at positions 5 and 6 are highly conserved in both halves of different CAP-binding sites, presumably in part because they facilitate kinking. 

The putative binding site for local anaesthetic molecules at the sodium channel has been identified as two amino acids in the sixth membrane-spanning segment of domain IV [2]. This binding site is located directly underneath the channel pore and can only be reached from the internal side of the membrane. Because local anaesthetics are applied exterior to the nerve fibre, they have to penetrate the axonal membrane before they can bind to the channel. 

TTX) and saxitoxin, which block the channel pore from the outer side. The difference in TTX sensitivity among the sodium channels is caused by a single amino acid difference in the P region of repeat I (phenylalanine or tyrosine in TTX-sensitive channels cysteine or serine in TTX-resistant channels). The S6 segments contribute to forming the inner pore of the channel and binding sites for local anesthetics. 

Barton and coworkers have shown that proteins can in fact modulate the DNA electron transfer [168]. Methyltransferases are enzymes that recognize distinct DNA sequences, e.g., 5 -G CGC-3, and effect methylation by extrading the target base cytosine ( C) completely out of the DNA duplex while the remainder of the double helix is left intact. The methyltransferase Hha 1-DNA complex is a well-characterized example, revealing that the structure of the DNA is significantly but locally distorted [169,170]. In a recent study, Raj ski et al. used DNA duplex 20 containing the M.Hha I binding site between two oxidizable 5 -GG-3 sites [168] (Fig. 20). The duplex contains a complementary strand, selectively 5 -modified with a Rh intercalator that can function as a photooxidant. Upon... 

Several drugs, the most well-known being local anesthetics and histrionicotoxin (HTX) (28), bind to an allosteric site on the AChR (relative to the agonist binding site). Biochemically, this site is identified by high affinity binding of [ H]Hj2 HTX (Table I). It may be located at the ion channel and coordinates between several of... 

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