Loop conformers

RM Fine, H Wang, PS Shenkm, DL Yarmush, C Levmthal. Predicting antibody hypervariable loop conformations. II Minimization and molecular dynamics studies of MCP603 from many randomly generated loop conformations. Proteins 1 342-362, 1986. 

Q Zheng, R Rosenfeld, S Vajda, C DeLisi. Determining protein loop conformation using scahng-relaxation techniques. Protein Sci 2 1242-1248, 1993. 

RNA structures, compared to the helical motifs that dominate DNA, are quite diverse, assuming various loop conformations in addition to helical structures. This diversity allows RNA molecules to assume a wide variety of tertiary structures with many biological functions beyond the storage and propagation of the genetic code. Examples include transfer RNA, which is involved in the translation of mRNA into proteins, the RNA components of ribosomes, the translation machinery, and catalytic RNA molecules. In addition, it is now known that secondary and tertiary elements of mRNA can act to regulate the translation of its own primary sequence. Such diversity makes RNA a prime area for the study of structure-function relationships to which computational approaches can make a significant contribution. 

Figure 17.2 An example of prediction of the conformations of three CDR regions of a monoclonal antibody (top row) compared with the unrefined x-ray structure (bottom row). LI and L2 are CDR regions of the light chain, and HI is from the heavy chain. The amino acid sequences of the loop regions were modeled by comparison with the sequences of loop regions selected from a database of known antibody structures. The three-dimensional structure of two of the loop regions, LI and L2, were in good agreement with the preliminary x-ray structure, whereas HI was not. However, during later refinement of the x-ray structure errors were found in the conformations of HI, and in the refined x-ray structure this loop was found to agree with the predicted conformations. In fact, all six loop conformations were correctly predicted in this case. (From C. Chothia et al.. Science 233 755-758, 1986.)...

X-ray structure analysis demonstrated that the nonaromatic macrocyclc adopts a conformation which can be described as a loop conformation in which the whole macrocycle is twisted. 

Although [34]octaphyrin 80 fulfills Hiickel s rule, the II NMR spectrum indicates by the high-field shift of the methine protons that the system is nonaromatic. The X-ray structure analysis demonstrates clearly the reason for the lack of aromatic stabilization, namely the nonplanar loop conformation in which the whole macrocycle is twisted similarly to the [32]octaphyrin structure and which is also found for [36]octaphyrin and [40]decaphyrin structures (vide infra). 

According to Hiiekel s rule, turcasarin should not be aromatic, but even if the macrocycle should fulfill the (4n +2) rule for aromatic systems the lack of planarity due to the loop conformation would prevent aromatic stabilization. In fact, the existence of the loop conformation in which the whole macrocycle is twisted was demonstrated by X-ray structure analysis and NMR investigations. 

Fig. 57 Schematic comparison of chain conformations of the midblock for ABC and ABA triblocks. ABC triblock terpolymers (a) have bridge conformations only, whereas ABA triblock copolymers (b) have bridge and loop conformations. From [159]. Copyright 2002 Wiley...

Kettleborough, C.A., Saldanha, J., Heath, V.J., et al. (1991). Humanization of a mouse monoclonal-antibody by CDR-grafting—The importance of framework residues on loop conformation. Protein Eng., 4, 773-783. 

A instead of the 15 A in the closed loop conformation of the enzyme. In any case, selective inhibitor design for TIM appears to require de novo design as there are no leads known that interact with the Ala-Tyr region of the enzyme. 

Scheme 6 m-Amb as a Template to Induce a Loop Conformation in a Cyclic Peptide 69-72 ... 

A Piperazinedione-Based Template To Stabilize Loop Conformations in... 

Another example of a quantal repeat—but with considerable variation in sequence—is seen in the keratin-associated proteins (KAPs). In sheep, these display pentapeptide and decapeptide consensus repeats of the form G—G—Q—P—S/T and C-C-Q/R—P—S/T—C/S/T—C—Q—P/T—S, respectively (Parry et al., 1979). Some of the positions, as indicated by the presence of a consensus sequence, contain residues that occur much more frequently than others, but the absolute conservation of a residue in any position is not observed. The decapeptide consists of a pair of five-residue repeats closely related, but different to that displayed by the pentapeptide. Although the repeats have an undetermined structure, the similarity of the repeat to a sequence in snake neurotoxin suggests that the pentapeptides will adopt a closed loop conformation stabilized by a disulphide bond between cysteine residues four apart (Fig. 5 Fraser et al., 1988 Parry et al, 1979). Relative freedom of rotation about the single bond connecting disulphide-bonded knots would give rise to the concept of a linear array of knots that can fold up to form a variety of tertiary structures. The KAPS display imperfect disulphide stabilization of knots and have interacting... 

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