Binding architecture

C.A. Bewley, A.M. Gronenbom and G.M. Clote. Minor groove-binding architectural proteins structure, function, and DNA recognition. Annu. Rev. Biophys. Biomol. Struct. 27 (1998) 105-31. 

The biomechanical properties of bone critically depend on this hierarchical strnc-ture. The macro-scale organization of osteons and Haversian canals provides long bones with their characteristic mechanical anisotropy. The microscale porosity in bone is ideal for cell migration and vascularization, whereas the nano-scale featnres act as a cell and mineral binding architecture [5]. 

Information may be stored in the architecture of the receptor, in its binding sites, and in the ligand layer surrounding the bound substrate such as specified in Table 1. It is read out at the rate of formation and dissociation of the receptor—substrate complex (14). The success of this approach to molecular recognition ties in estabUshing a precise complementarity between the associating partners, ie, optimal information content of a receptor with respect to a given substrate. 

There is a second family of small lipid-binding proteins, the P2 family, which include among others cellular retinol- and fatty acid-binding proteins as well as a protein, P2, from myelin in the peripheral nervous system. However, members of this second family have ten antiparallel p strands in their barrels compared with the eight strands found in the barrels of the RBP superfamily. Members of the P2 family show no amino acid sequence homology to members of the RBP superfamily. Nevertheless, their three-dimensional structures have similar architecture and topology, being up-and-down P barrels. 

FIGURE 22.19 The molecular architecture of PSII. The core of the PSII complex consists of the two polypeptides (D1 and D2) that bind P680, pheophytin (Pheo), and the quinones, Qb- Additional components of this complex include cytochrome -6559,... 

Ryanodine Receptor. Figure 1 Three-dimensional architecture of the RyR1 by cryo-electron microscopy, (a), top view (from the T-tubule) (b), bottom view (from the SR lumen) (c), side view (parallel to the SR membrane). The binding sites of FKBP12, apo-CaM and Ca -CaM are indicated in the side view. Courtesy of Dr. M. Samso (modified from Samso etal. (2005) Nat Struct Mol Biol 12 539-544). 

Liu S, Kiick KL (2008) Architecture effects on the binding of cholera toxin by helical glycopolypeptides. Macromolecules 41 764—772... 

The crystal structure of the HNL isolated from S. bicolor (SbHNL) was determined in a complex with the inhibitor benzoic acid." The folding pattern of SbHNL is similar to that of wheat serine carboxypeptidase (CP-WII)" and alcohol dehydrogenase." A unique two-amino acid deletion in SbHNL, however, is forcing the putative active site residues away from the hydrolase binding site toward a small hydrophobic cleft, thereby defining a completely different active site architecture where the triad of a carboxypeptidase is missing. 

Of all the known sites for metal-ion binding to the heteroatoms of DNA bases, G-N3 is the most elusive. The adjacent 2-amino group is often considered to offer steric hindrance to binding at this site. However, while this undoubtedly influences the chemistry it does not preclude binding. The tri-metalated [ [Pt(N]3(9-Et G N1,N3,N7)]5 compound has for many years been the only structurally characterized example of an N3-coordinated guanine (66). A second example has now been reported, the tetranuclear octacation 16 (56). In this complex both the N7 and N3 atoms are bound to Pd2+ (Fig. 22). The molecule presents an interesting new architecture for a guanine-tetramer. Such structures are well known in DNA chemistry and are almost inevitably metal-ion stabilized (67,68). 

Macrocyclic receptors made up of two, four or six zinc porphyrins covalently connected have been used as hosts for di- and tetrapyridyl porphyrins, and the association constants are in the range 105-106 M-1, reflecting the cooperative multipoint interactions (84-86). These host-guest complexes have well-defined structures, like Lindsey s wheel and spoke architecture (70, Fig. 27a), and have been used to study energy and electron transfer between the chromophores. A similar host-guest complex (71, Fig. 27b) was reported by Slone and Hupp (87), but in this case the host was itself a supramolecular structure. Four 5,15-dipyridyl zinc porphyrins coordinated to four rhenium complexes form the walls of a macrocyclic molecular square. This host binds meso-tetrapyridyl and 5,15-dipyridyl porphyrins with association constants of 4 x 107 M-1 and 3 x 106 M-1 respectively. 

Hawthorne and co-workers have also produced a series of macrocyclic Lewis acid hosts called mercuracarborands (156, 157, and 158) (Fig. 84) with structures incorporating electron-withdrawing icosahedral carboranes and electrophilic mercury centers. They were synthesized by a kinetic halide ion template effect that afforded tetrameric cycles or cyclic trimers in the presence or absence of halide ion templates, respectively.163 These complexes, which can bind a variety of electron-rich guests, are ideal for catalytic and ion-sensing applications, as well as for the assembly of supramolecular architectures. 

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