Buried protein atoms

For each fold one searches for the best alignment of the target sequence that would be compatible with the fold the core should comprise hydrophobic residues and polar residues should be on the outside, predicted helical and strand regions should be aligned to corresponding secondary structure elements in the fold, and so on. In order to match a sequence alignment to a fold, Eisenberg developed a rapid method called the 3D profile method. The environment of each residue position in the known 3D structure is characterized on the basis of three properties (1) the area of the side chain that is buried by other protein atoms, (2) the fraction of side chain area that is covered by polar atoms, and (3) the secondary stmcture, which is classified in three states helix, sheet, and coil. The residue positions are rather arbitrarily divided into six classes by properties 1 and 2, which in combination with property 3 yields 18 environmental classes. This classification of environments enables a protein structure to be coded by a sequence in an 18-letter alphabet, in which each letter represents the environmental class of a residue position. 

In soluble globular proteins, hydrophilic amino acids tend to be on the exterior of the molecule whereas hydrophobic amino acids are packed in the interior [13]. To quantitatively describe the location of an amino acid in relation to the protein surface, different measures of solvent exposure have been developed. In the present context, the solvent exposure is modeled by the number s of protein atoms that are within a sphere of radius R centered at the position of atom c of amino acid a [5]. If the amino acid is buried in the protein interior, s is large because the surrounding volume is (almost) completely filled by protein atoms. On the other hand, if the amino acid is exposed, part of the volume is occupied by solvent molecules, which results in a smaller s (see Table 11.1 and Figure 11.3). Again, relative frequencies fac(s) and fc(s) are derived from the database and the net potential for solvent exposure is then... 

Bound solvent molecules are an integral part of the structures of their proteins. This is seen in the extensive hydrogen bond networks that they form and that bridge protein atoms. Such cross-linking is observed internally as well as externally many globular proteins contain a number of buried water molecules. The water molecule is unique because it has both double-donor and double-acceptor capability. 

Each interface contains 11 or 12 hydrogen bonds or salt bridge interactions. Although the GH/GHR complex buries more surface area into its interface, it stiU contains only 12 specific interactions. Three of the IFN-7/ IFN-7RI interactions occur between mainchain atoms in the AB loop of IFN-7 and the L2 loop of IFN-7RI. In addition to the 12 receptor-cytokine interactions, seven water molecules bridge the donor and acceptor groups of IFN-7 and IFN-7RI via hydrogen bonds (Randal and Kossiakoff, 2001). Since the B-factors for the water and protein atoms in the complex are essentially the same, the water molecules are considered to be an integral part of the interface. The presence of ordered water molecules in the IFN-7/IFN-7RI interface is not likely unique, since the IL-lO/IL-lORl interface is even more polar. However, the poorer diffraction quality of IL-10 complex crystals ( 2.9A versus 2.0A) obtained at this time prevents a detailed description of the interfacial waters. The water molecules in the... 

The Voronoi calculation can be performed on protein atoms buried at interfaces as well as inside proteins. However, the procedure has a serious limitation a Voronoi polyhedron can be drawn around an atom only if it is completely surrounded by other atoms. At interfaces, only about one-third of the atoms that contribute to the interface area B have zero accessible surface area. These atoms are located mostly at the center of the interface, which biases the F/Fq ratio in an opposite way to the gap index, which is biased toward the periphery. However, high-resolution X-ray structures usually report positions for immobilized water molecules, which are abundant at interfaces (see Section II,D). These molecules may also be used to close the polyhedra, making the evaluation of Voronoi volumes possible for atoms which are surrounded by both protein atoms and immobilized water molecules (Fig. 4). On average, there are as many such interface atoms as there are completely buried atoms. Thus, a Voronoi calculation taking into account the crystallographic water molecules applies to two-thirds of the interface atoms on average instead of only one-third and up to 90% in specific cases (Lo Conte et al., 1999). 

The Voronoi volume calculation was also carried out for protein atoms at protein-DNA interfaces in 28 high-resolution structures of protein-DNA complexes by Nadassy et al. (1999). The coordinate files also contain water positions, and volume calculations were performed in the presence of these water molecules. Fifty-seven percent of the interface protein atoms could be included and the V/Vq ratios were found to spread over a narrow range of 0.97-1.04, with a mean of 1.01 (Fig. 5, bottom). Thus, the atomic packing is very similar to that found for protein-protein interfaces. Omitting water molecules from the calculations yielded a broader range (0.94-1.1) and many fewer buried interface atoms. Thus, water molecules once more play a key role in fostering efficient packing at protein-nucleic acid interfaces. 

In general, the CSRs were found to be 4-26 residues long. They most often correspond to correctly predicted secondary-structure elements, which frequently occur at the polypeptide chain ends and are nearly always buried, making extensive contacts with other protein atoms in the native structure. This is all the more remarkable that these consensus regions were not selected on the basis of hydrophobicity, buried surface area, or position in the three-dimensional structure. Rather... 

Figure 9 Backbone (Ca, C, N) trace from residues 83 to 250 of 30 conformers of inhibited sfSTR. Residues 251 to 255 are disordered and are not included. All the heavy atoms of the inhibitor are shown. The family of structures are viewed along the long axis of the catalytic helix B. The inhibitor (I) binds to the protein in a well-defined cleft and runs antiparallel to the outer strand of the p-sheet with the ring of Pf homophenylalanine (hP) buried in a bottomless S/ subsite and the 2 arginine (R) is exposed to the solvent. 

Various spectroscopic methods have been used to probe the nature of the copper centers in the members of the blue copper oxidase family of proteins (e.g. see ref. 13). Prior to the X-ray determination of the structure of ascorbate oxidase in 1989, similarities in the EPR and UV-vis absorption spectra for the blue multi-copper oxidases including laccase and ceruloplasmin had been observed [14] and a number of general conclusions made for the copper centers in ceruloplasmin as shown in Table 1 [13,15]. It was known that six copper atoms were nondialyzable and not available to chelation directly by dithiocarbamate and these coppers were assumed to be tightly bound and/or buried in the protein. Two of the coppers have absorbance maxima around 610 nm and these were interpreted as blue type I coppers with cysteine and histidine ligands, and responsible for the pronounced color of the protein. However, they are not equivalent and one of them, thought to be involved in enzymatic activity, is reduced and reoxidized at a faster rate than the second (e.g. see ref. 16). There was general concurrence that there are two type HI... 

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