Native protein structures

Most potential energy surfaces are extremely complex. Fiber and Karplus analyzed a 300 psec molecular dynamics trajectory of the protein myoglobin. They estimate that 2000 thermally accessible minima exist near the native protein structure. The total number of conformations is even larger. Dill derived a formula to calculate the upper bound of thermally accessible conformations in a protein. Using this formula, a protein of 150 residues (the approx-... 

The complex hierarchy of native protein structure may be disrupted by multiple possible destabilizing mechanisms. As has been described in the foregoing, these processes may disrupt noncovalent forces of interaction or may involve covalent bond breakage or formation. A summary of the processes involved in the irreversible inactivation of proteins is illustrated in Fig. 3 and described briefly in the following section. Detailed discussions of mechanisms of protein desta-... 

Fedorov, A. N., and Baldwin, T. O. (1995). Contribution of co-translational folding to the rate of formation of native protein structure. Proc. Natl. Acad. Sci. USA 92, 1227—1231. 

The following protocol for passive adsorption is based on methods reported for use with hydrophobic polymeric particles, such as polystyrene latex beads or copolymers of the same. Other polymer particle types also may be used in this process, provided they have the necessary hydrophobic character to promote adsorption. For particular proteins, conditions may need to be optimized to take into consideration maximal protein stability and activity after adsorption. Some proteins may undergo extensive denaturation after immobilization onto hydrophobic surfaces therefore, covalent methods of coupling onto more hydrophilic particle surfaces may be a better choice for maintaining native protein structure and long-term stability. 

Many amyloid fibrils seem to be made up of smaller protofilaments. Although the number of protofilaments per fibril varies, the protofilaments have a fairly consistent diameter of 30 A (Serpell et al., 2000b Shirahama and Cohen, 1967 Shirahama et al., 1973). For some proteins, for example TTR, the protofilament diameter matches that of the native protein, suggesting that a Gain-of-Interaction model is plausible (Serpell et al., 1995). For other proteins, for example the SH3 domain, the protofilament seems too small to accommodate the native protein structure, suggesting that a Refolding model is plausible (Jimenez et al., 1999). 

The first problem encountered once the peptide has been successfully synthesized is that standard purification protocols fail. Although very hydrophobic peptides are soluble in acids such as TFA, these harsh conditions are not suitable for purification, because they can reduce column life times and denature native protein structures. Hence residual acid has to be removed, and many peptides can then be redissolved in mixtures of water and tert-butanol. Peptides with a strong tendency to aggregate may be dissolved either in trifluoroethanol (TFE), hexafluoroisopropanol (HFIP), mixtures of 1-propanol and 1-butanol, 20% acetic acid or 70-90% formic acid. 

Formation of protein gel structures can occur under conditions which disrupt the native protein structure provided that the protein concentration, thermodynamic conditions and other conditions are optimal for the formation of the tertiary matrix. The most Important food processing techniques relative to protein gelation Involve divalent cations (calcium) and/or heat treatment. 

Addition of 20-25% (v/v) ethylene glycol, known to stabilize native protein structures, has often been found to be a convenient measure also for phytochrome. Absorption spectroscopy showed that the additive does not cause any loss of Pr fcf Pfr photochromicity, and the lifetimes and amplitudes of the Pj components [108] as well as the kinetic parameters of the absorption decays of 1 qq and I200 [113] at 272-297 K (Table 3) were hardly affected either. This is in accord with a confinement of the sequence Pr - I700 - Ibi t0 the phytochromobilin-binding protein domain without... 

Yes. Any change that destroys native protein structure without hydrolyzing the chain is a denaturation. 

S. Miyazawa, R.L. Jemigan, Long- and short-range interactions in native protein structures are consistent/minimally frustrated in sequence space. Proteins 50, 35—43 (2003)... 

Amyloid fibrils are non-native protein structures that demonstrate a host of desirable properties, making these fibers attractive components for... 

Cold stress may induce synthesis of heat-shock (stress) proteins. Exposure of cells to cold shock may lead to the induction of one or more of the classes of molecular chaperones that also are induced by heat shock. This is strong evidence that low temperature, like high temperature, can lead to non-native protein structures in vivo and, therefore, to the requirement for enhanced chaperoning activity. Induction of cold-induced protein chaperones has been seen in bacteria (Salotra et al., 1995), in whole organism studies of ectothermic animals (Petersen et al., 1990 Yocum et ah, 1991),... 

Recently, it was hypothesized that native protein structure is specified by a stereochemical code (1). We have been evaluating this hypothesis by examining high resolution protein structures to extract recurrent patterns and identify formative interactions (2,3). Many patterns are smeill enough to be analyzed exhaustively by conformational search techniques. 

Structure comparison methods are a way to compare three-dimensional structures. They are important for at least two reasons. First, they allow for inferring a similarity or distance measure to be used for the construction of structural classifications of proteins. Second, they can be used to assess the success of prediction procedures by measuring the deviation from a given standard-of-truth, usually given via the experimentally determined native protein structure. Formally, the problem of structure superposition is given as two sets of points in 3D space each connected as a linear chain. The objective is to provide a maximum number of point pairs, one from each of the two sets such that an optimal translation and rotation of one of the point sets (structural superposition) minimizes the rms (root mean square deviation) between the matched points. Obviously, there are two contrary criteria to be optimized the rms to be minimized and the number of matched residues to be maximized. Clearly, a smaller number of residue pairs can be superposed with a smaller rms and, clearly, a larger number of equivalent residues with a certain rms is more indicative of significant overall structural similarity. 

The results of the electrolytic reduction showed that the disulfide bridge is necessary for the enzymic activity. This does not imply, however, that it should be directly involved in the catalytic mechanism. The disulfide bond most likely only helps to keep the native protein structure intact. 

Enzymes are not catalytically active if water is completely absent. The often cited explanation is that at least a monolayer of water per enzyme molecule is necessary to keep the enzyme active [40]. Apparently, the essential noncova-lently bound water maintains the enzyme s native protein structure. In an enzymatic reaction under supercritical conditions, the water partitions between the enzyme, the enzyme support and the reaction mixture. In an essentially non-aqueous system, the existing water partitions preferrably to the solvent with increasing hydrophilicity. If there is little water in the system and if the solvent is relatively hydrophilic, the solvent may strip the essential water from the enzyme, making it inactive. When Zaks and Klibanov first noted that enzymes were more active in hydrophobic solvents than in hydrophilic organic solvents. 

An understanding of the mechanism by which a polypeptide chain folds from the denatured coil state to the native protein structure remains an elusive goal of structural biology. Despite considerable effort, both theoretical and experimental, we are still not able to give a detailed mechanistic description of any such folding process." Within a cell, myriads of amino-acid sequences fold effortlessly into precise 3D structures, yet at present no algorithm exists which can identify the lowest free energy state for a protein under the conditions of the cell, due to various complications. 

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