Protein cont structure

Lo Conte, L., Chothia, C and Janin, J. (1999) The atomic structure of protein-protein recognition sites../. Mol. Biol. 285,2177-2198. 

The Protein Data Bank (PDB) is the primary structure database serving as the international repository for the processing and distribution of 3D structures of biomacromolecules (Bernstein et al, 1977). The database is operated by the Research Collaboratory for Structural Bioinformatics (RCSB) and is accessible from the primary RCSB site at http //www.rcsb.org/pdb/ (Berman et al., 2000). Most of the structure fold/motif/domain databases (Conte et al., 2000) and analysis servers (Brenner et al, 2000 Hofmann et al, 2000 Kelley et al., 2000 Shi et al., 2001) utilize 3D-structure information from PDB and sequence information from primary sequence databases. Some of these databases/analysis servers and their URL are listed in Table 12.3. 

In the most comprehensive structural analysis to date, Lo Conte et al.11 studied 75 protein-protein complexes comprising 24 protease-inhibitor, 19 antibody-antigen, and 32 other complexes (including 9 further enzyme-inhibitor and 11 signal transduction complexes). The authors found that protein-protein interfaces typically have a size of 1600 400 A2 with a few complexes exhibiting very large (2000—4660 A2) or very small (less than 1000 A2) interfaces. With respect to their chemical nature, the interfaces were found to... 

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). 

In the 75 protein-protein complexes of Lo Conte et al. (1999), 96% of the interfaces have V/Vq in the range 0.97-1.06. Thus, the packing of atoms buried at protein-protein interfaces is very similar to that of the protein interior. In 36 complexes with X-ray structures at a resolution of 2.5 A and better, the V/Vq ratios calculated in the presence of water molecules were distributed over a narrow range of 0.97-1.03 (Fig. 5, top). Therefore, their interfaces are packed like the protein core, except that water, which is almost entirely excluded from the protein core, makes an important contribution to the packing at protein-protein interfaces. There is one exception to this rule in the sample analyzed by Lo Conte et al. (1999) the complex between cytochrome peroxidase and cytochrome c [PDB code, Iccp (Pelletier and Kraut, 1992)]. Its interface is small and has only a few buried atoms and a large volume ratio (1.07). In contrast, the 19 protease-inhibitor and the 19 antigen-antibody complexes of this sample have mean V/Vq ratios of 1.00 and 1.01, respectively. Thus, unlike 5c and the gap index, the volume ratio indicates that these two types of interfaces are close-packed and shows no difference in their packing density, at least for their buried atoms. 

Protein-protein and protein-DNA complexes with X-ray structures at 2-A resolution or better listed in Lo Conte et al. (1999) and Nadassy et al. (1999). 

Three interfaces in the sample of 75 complexes of Lo Conte et al. (1999) have B 1150 A, just below the range 1200-2000 A dehning the standard size. The distinction may be spurious, due to experimental error or to missing contacts. In two of the crystal structures, one of the components is not the complete protein, and, therefore, the interface may be incomplete as in the HIV gp 120-CD4-Fab 27 crystal. These are the complex of a domain of Che A with Che Y [PDB code, laOo (Welch et al., 1998)], implicated in the two-component system of bacterial signal transduction, and the complex of a domain of the HIV capsid protein with cyclophilin [PDB code, lak4 (Gamble etal., 1996)]. 

Lo Conte. L. Ailey. B. Hubbard. T.J.P., et al. SCOP A structural classification of proteins database. Nucleic Acids... 

L. Lo Conte, C. Chothia, and J. Janin,/. Mol. Biol., 285, 2177-2198 (1999). The Atomic Structure of Protein-Protein recognition Sites. 

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