Folded Protein Structures

Because globular proteins have nonrepeating structures, it is essential to have a means for displaying the entire three-dimensional structure in sufficient detail, and yet not too much detail, so that the overall structural design can be appreciated. 

The primary data of protein crystallography yield a three-dimensional electron-density map, which must be interpreted in terms of a three-dimensional model of all atom positions in the protein. Such modeling is usually done by computer graphics. 

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Thirumalai D and Klimov D K 2000 Emergence of stable and fast folding protein structures Stochastic... 

With the development of NMR-based experiments for studying folded proteins, structural analysis of denatured proteins entered a new phase (Wuthrich, 1994 Dobson et al., 1994 Shortle, 1996). Whereas other spectroscopies and hydrodynamic studies give data that correspond to a complex sum of the properties of all residues, NMR spectroscopy extracts information about individual residues. For the first time, local structural features could be directly inferred from the behavior of sets of residues along the sequence. 

Fig. 5. Subdivisions of the phi/psi or Ramachandran map labeled with the range of propensities for the 18 amino acids (glycine and proline are excluded) as they map to each subdivision calculated from a large collection of folded protein structures. The propensity is defined by the probability that amino acid x will be found in a subdivision divided by the probability that an average amino acid will be found in a subregion. Data are taken from Table 1 of Shortle (2002).

Figure 1. Model of a folded protein structure (A) and of a detail representing a (chiral) binding domain for a ligand (guest) molecule (B). Intermolccular interaction areas are symbolized and include van der Waals interrelations.

Visualizing Folded Protein Structures Primary Structure Determines Tertiary Structure Secondary Valence Forces Are the Glue That Holds Polypeptide Chains Together Domains Are Functional Units of Tertiary Structure Predicting Protein Tertiary Structure Quaternary Structure Involves the Interaction of Two or More Proteins... 

Van der Waals Forces. Van der Waals interactions are of two types one attractive and one repulsive. Attractive van der Waals forces involve interactions among induced dipoles that arise from fluctuations in the electron charge densities of neighboring nonbonded atoms. Such interactions amount to 0.1-0.2 kcal/mol despite their small size, the large number of such interactions that occur when molecules come close together makes such interactions quite significant. Van der Waals forces favor close packing in folded protein structures. 

Domain. A segment of a folded protein structure showing conformational integrity. A domain can comprise the entire protein or just a fraction of the protein. Some proteins, such as antibodies, contain many structural domains. 

Fund., Genet., 23, 536 (1995). Atomic and Residue Hydrophilicity in the Context of Folded Protein Structures. 

Protein crystal growth involves the incorporation of a complex unit into an existing lattice. The growth unit usually includes the covalent polypeptide chain, water molecules that are integral components of the folded protein structure, and additional water molecules and solvent ions that may become immobilized at crystal lattice contacts. Direct inter-... 

It has been noted that water molecules are involved in establishing intramolecular hydrogen-bonding interactions between protein atoms and thus serves as an integral part of the folded protein structure. The effect of the water molecules on simulated THz spectra of the thioredoxin was investigated, since water can substantially affect the dynamics of the thioredoxin. To do this, an explicit simulation of water molecules was also conducted using a more advanced model which is described below. 

Phospholipids located in a membrane, phospholipids (as second messengers) in the cytosol, sphingomyelin, folded protein structures, reactive sites of enzymes, nucleic acids in the zinc finger of the chromosome. Wliat are tire assumptions and constraints for each of these molecular modeling systems (a) Force field methods, (b) Semi-empirical method, (c) Ab initio method. 

Thirumalai D and Klimov D K 2000 Emergence of stable and fast folding protein structures Stochastic Dynamics and Pattern Formation in Biological and Complex Systems ed S Kim, K J Lee and W Sung (Melville, NY American Institute of Physics) pp 95-111... 

The Log-normal analysis method shows also that binding of calcofluor at high concentrations disrupts the protein structure. This method is very sensitive to the modifications occurring around the fluorophore. In fact, in presence of folded protein structure, the calculated emission spectrum fits perfectly the experimental one (Fig. 8.33). However, when the structure of the protein is altered, we obtain a calculated spectrum that is different from the experimental one (Fig. 8.34, spectrum b, max 337 nm). Also, in this case, we can derive two other emission spectra that correspond to the hydrophobic (kmax 330 nm) and surface Trp residues ( max 355 nm). This deconvolution is not possible in the presence of a compact protein (Fig. 8.33). Therefore, the Log-normal analysis allows comparing disrupted and compact proteins with two or three classes of Trp residues, since in the case of a compact protein the analysis gives a result identical to that obtained for a free tryptophan in solution. 

Using myoglobin and porin as examples, describe the main characteristics of native folded protein structures. 

Fig. 7.3. The PP fold protein structure found in avian pancreatic polypeptide (APP) and related peptides.

Dinuclaotida fold a characteristic folded protein structure constituting part or all of the structure of four NAD-dependent dehydrogenases, and certain other enzymes, some of which do not bind nucleotides. The D.f. was first identified in the tertiary structures of liver alcohol dehydrogenase (EC l.l.l.l), gly-... 

Matter, 15, S1787 (2003). Tubes near the Edge of Compactness and Folded Protein Structures. 

Gene Expression, regulation of Immunology— Autoimmunity Mammalian Cell Culture Metabolic Engineering Nucleic Acid Synthesis Protein Folding protein Structure Protein Synthesis Tissue Engineering translation of RNA TO Protein... 

Cell Death (Apoptosls) Gene Expression, Regulation OF Immunology-Autoimmunity Protein Folding Protein Structure Ribozymes Translation OF RNA TO Protein... 

D. Thirumalai and D. K. Klimov, Emergence of stable and fast folding protein structures, in S. Kim, K. J. Lee, and W. Sung, eds.. Stochastic Dynamics and Pattern Forttmtion in Biological Systems, American Institute of Physics, New York, 2000, pp. 95-111. 

Fig. 10. Schematic conformation of sperm whale myoglobin after Kendtew et al. (48). The sausage is the protein chain, which is mostly in the a-hdical conformation. The heme group is held in a cleft by apolar contacts, and by two histidine side chmns. Three or four other histidine side chains participate in the fcxmaticm the folded protein structure. Since the side chain of histidine contains an imidazole ring, a free side chain can be protonated at low pH (the pK is ca. 6.5). However, the five or six buried side chains cannot be protonated, and hence the overall equilibrium constant for unfolding is strongly pH dependent in first approximation (34)...

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