Loop flexibility

Arold S, O Brien R, Eranken P, Strub MP, Hoh E, Dumas C, Lad-bury JE. RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef. Biochemistry 1998 37 14683-14691. Inga A, Monti P, Eronza G, Darden T, Resnick MA. p53 mutants exhbiting enhanced transcriptional activation and altered promoter selectivity are revealed using a sensitive, yeast-based functional assay. Oncogene 2001 20 501-513. 

Kamerltn SC, Rucker R, Boresch S (2007) A molecular dynamics study of WPD-loop flexibility in PTPIB. Biochem Biophys Res Commiin 356 1011—1016... 

Osborne, M., Schnell, J., Benkovic, S., Dyson, H. and Wright, P. (2001). Backbone dynamics in dihydrofolate reductase complexes role of loop flexibility in the catalytic mechanism. Biochemistry 40, 9846-9859... 

Figure 5.10 Millisecond HX kinetics revealing loop dynamics in native cytochrome c. (Left) The observed rate for each loop Is compared to the chemical exchange rate in order to generate a segment-averaged protection factor. (Right) Loop flexibility of cytochrome c, mapped on to pdb lAKK [53], with darkest to lightest gray indicating least to most flexibility. Reproduced with permission from Ref [21]. 2012, American Chemical Society. (See insert for color representation of the figure.)...

R. C. Wade, M. E. Davis, B. A. Luty, J. D. Madura, and J. A. McCammon. Gating of the active site of triose phosphate isomerase Brownian dynamics simulations of flexible peptide loops in the enzyme. Biophys. J., 64 9-15, 1993. 

There are eight types of inert lUDs used around the world two are unmedicated and six are copper. Outside of China, the Lippes Loop, made of polyethylene, is the most widely used unmedicated lUD. The other main type of unmedicated lUD, used mostiy in China, is a flexible stainless steel ring, ie, the Chinese lUD. 

Engines are also designed to use either gasoline or methanol and any mixture thereof (132—136). Such a system utilizes the same fuel storage system, and is called a flexible fueled vehicle (EEV). The closed loop oxygen sensor and TWC catalyst system is perfect for the flexible fueled vehicle. Optimal emissions control requires a fuel sensor to detect the ratio of each fuel being metered at any time and to correct total fuel flow. 

In some cases, whole parts of the protein are missing from the experimentally determined structure. At times, these omissions reflect flexible parts of the molecule that do not have a well-defined structure (such as loops). At other times, they reflect parts of the molecule (e.g., terminal sequences) that were intentionally removed to facilitate the crystallization process. In both cases, structural models may be used to fill in the gaps. 

The secondary structure elements, formed in this way and held together by the hydrophobic core, provide a rigid and stable framework. They exhibit relatively little flexibility with respect to each other, and they are the best-defined parts of protein structures determined by both x-ray and NMR techniques. Functional groups of the protein are attached to this framework, either directly by their side chains or, more frequently, in loop regions that connect sequentially adjacent secondary structure elements. We will now have a closer look at these structural elements. 

Long loop regions are often flexible and can frequently adopt several different conformations, making them "invisible" in x-ray structure determinations and undetermined in NMR studies. Such loops are frequently involved in the function of the protein and can switch from an "open" conformation, which allows access to the active site, to a "closed" conformation, which shields reactive groups in the active site from water. 

Serpins form very tight complexes with their corresponding serine pro-teinases, thereby inhibiting the latter. A flexible loop region of the serpin binds to the active site of the proteinases. Upon release of the serpin from the complex its polypeptide chain is cleaved by the proteinase in the middle of this loop region and the molecule is subsequently degraded. In addition to the active and cleaved states of the serpins there is also a latent state with an intact polypeptide chain that is functionally inactive and does not bind to the proteinase. 

The setpin fold comprises a compact body of three antiparallel p sheets, A, B and C, which ate partly coveted by a helices (Figure 6.22). In the structure of the uncleaved form of ovalbumin, which can be regarded as the canonical structure of the serpins, sheet A has five strands. The flexible loop starts at the end of strand number 5 of p sheet A (plS in Figure 6.22), then... 

The flexible loop region in the active form of antithrombin (Figure 6.23a) is in the same general position as in ovalbumin but the first few residues form a short sixth p strand in p sheet A inserted between strands pS and pis. Furthermore there is no a helix in the loop which is extended outside the main body of the molecule, ready to be inserted into the active site of thrombin. 

In viw PAI and antithrombin are stabilized in their active forms by binding to vitronectin and heparin, respectively. These two serpins seem to have evolved what Max Perutz has called "a spring-loaded safety catch" mechanism that makes them revert to their latent, stable, inactive form unless the catch is kept in a loaded position by another molecule. Only when the safety catch is in the loaded position is the flexible loop of these serpins exposed and ready for action otherwise it snaps back and is buried inside the protein. This remarkable biological control mechanism is achieved by the flexibility that is inherent in protein structures. 

In the structure of unphosphorylated phosducin that binds to Gpy, Ser 73 points towards the flexible loop of phosducin and not towards Gpy it is, therefore, accessible on the surface for phosphorylation. Phosphorylation of Ser 73 cannot lead to the direct disruption of the phosducin/GpY interaction. Rather, the structure suggests that phosphorylation may lead to conformational changes in the N-terminal domain of phosducin, especially in the flexible loop region, that could weaken or alter the phosducin/GpY interface. 

A helix-loop-helix motif is a DNA-binding motif, related to the leucine-zipper. A helix-loop-helix motif consists of a short a helix, connected by a loop to a second, longer a helix. The loop is flexible and allows one helix to fold back and pack against the other. The helix-loop-helix structure binds not only DNA but also the helix-loop-helix motif of a second helix-loop-helix protein forming either a homodimer or a heterodimer. 

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