Protein structural flexibility

R314 P. Cioni and E. Gabellieri, Protein Dynamics and Pressure What Can High Pressure Tell Us about Protein Structural Flexibility , Biochim. Biophys. Acta, Proteins Proteomics, [online computer file], 2011, 1814, 934. 

A, C W Murray, D E Clark, D R Westhead and M D Eldridge 1998. Flexible Docking using Tabu rch and an Empirical Estimate of Binding Affinity. Proteins Structure, Function and Genetics 167-382. 

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. 

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. 

The thermodynamic stability of a protein in its native state is small and depends on the differences in entropy and enthalpy between the native state and the unfolded state. From the biological point of view it is important that this free energy difference is small because cells must be able to degrade proteins as well as synthesize them, and the functions of many proteins require structural flexibility. 

For the known nickel sites in biological systems, four-coordinate square planar, five-coordinate, and six-coordinate octahedral geometries are found.1840-1846 In general, the flexible coordination geometry of nickel causes its coordination properties in metallo-biomolecules to be critically influenced by the protein structure. 

Mizuno H, Mai TR, Walchli M, Rikuchi A, Fukano T, Ando R, Jeyakanthan J, Taka J, Shiro Y, Ikura M, Miyawaki A (2008) Light-dependent regulation of structural flexibility in a photochromic fluorescent protein. Proc Natl Acad Sci USA 105 9227-9232... 

The description of protein structure as presented thus far may lead to the conclusion that proteins are static, rigid structures. This is not the case. A protein s constituent atoms are constantly in motion, and groups ranging from individual amino acid side chains to entire domains can be displaced via random motion by anything up to approximately 0.2 nm. A protein s conformation, therefore, displays a limited degree of flexibility, and such movement is termed breathing . 

For proteins the X-ray structures usually are not determined at high enough resolution to use anisotropic temperature factors. Average values for B in protein structures range from as low as a few A2 for well-ordered structures to 30 A2 for structures involving flexible surface loops. Using equation 3.6, one can calculate the root mean square displacement fu2 for a well-ordered protein structure at approximately 0.25 A (for B = 5 A2) and for a not-so-well-ordered structure at... 

Recently, several CYP crystal structures have been deposited in the P D B and could be used to understand the different metabolic properties. From the analysis of the different protein structures, it could be concluded that in general CYPs maintain the secondary elements across the different subfamilies, but they have a quite high flexibility, accommodating the protein structures to the ligand bound in the enzyme cavity. 

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