Database homologous proteins

Homologous proteins have similar three-dimensional structures. They contain a core region, a scaffold of secondary structure elements, where the folds of the polypeptide chains are very similar. Loop regions that connect the building blocks of the scaffolds can vary considerably both in length and in structure. From a database of known immunoglobulin structures it has, nevertheless, been possible to predict successfully the conformation of hyper-variable loop regions of antibodies of known amino acid sequence. 

The World Wide Web has transformed the way in which we obtain and analyze published information on proteins. What only a few years ago would take days or weeks and require the use of expensive computer workstations can now be achieved in a few minutes or hours using personal computers, both PCs and Macintosh, connected to the internet. The Web contains hundreds of sites of Interest to molecular biologists, many of which are listed in Pedro s BioMolecular Research Tools (http // www.fmi.ch/biology/research tools.html). Many sites provide free access to databases that make it very easy to obtain information on structurally related proteins, the amino acid sequences of homologous proteins, relevant literature references, medical information and metabolic pathways. This development has opened up new opportunities for even non-specialists to view and manipulate a structure of interest or to carry out amino-acid sequence comparisons, and one can now rapidly obtain an overview of a particular area of molecular biology. We shall here describe some Web sites that are of interest from a structural point of view. Updated links to these sites can be found in the Introduction to Protein Structure Web site (http // WWW.ProteinStructure.com/). 

Similar residues in the cores of protein structures especially hydrophobic residues at the same positions, are responsible for common folds of homologous proteins. Certain sequence profiles of conserved residue successions have been identified which give rise to a common fold of protein domains. They are organized in the smart database (simple modular architecture research tool) http //smait.embl-heidelberg.de. 

InterPro (http //www.ebi.ac.uk/interpro), database of protein families, domains, and functional sites allows prediction of the function or structure of a new protein on the basis of its sequence homology to sequences of known proteins. 

Mizuguchi, K., Deane, C. M., Blundell, T. L., and Overington, J. P. (1998) HOMSTRAD a database of protein structure alignments for homologous families. 

Advancements in crystallography/NMR techniques have resulted in an exponential increase in the number of protein structures in publicly available structural databases (e.g., as of September 2009, the Protein Database Bank PDB contains experimentally solved 3D structural data for 60,000 structures (www.pdb.org)). In addition, several structural genomics consortiums aim to provide crystal structures across all protein families (38). In case when experimental structures are not available, techniques such as homology modeling are often used to build structural models of other homologous proteins (21). 

PALI (Phylogeny and Alignment of Homologous Protein Domains) Database. The PALI (v 2.6) database provides three-dimensional structure-based sequence alignments for homologous proteins of known three-dimensional structure (24-26). The protein families have been derived from the SCOP (Structural Classification of Proteins) database (27). There are 2,518 protein families, and using more than one sequence as reference, 37,986 profiles have been generated. 

Balaji S, Sujatha S, Knmarm SS et al (2001) PALI-a database of Phylogeny and ALIgnment of homologous protein structures. Nucleic Acids Res 29 61-65... 

Clauser et al. 1999). However, there remain several limitations. The lack of complete and accurately annotated databases limits the quality of matches that can be achieved. The greater number of highly homologous proteins in higher organism complicates the distinguishing between closely related proteins. Last but not least, information of peptide sequences and sites of modifications cannot be deduced from PMF measurements. 

Mewes HW, Albermann K, Bahr M, Frishman D, Gleissner A, Hani J, Heuman K, Kleine K, Maierl A, Oliver SG, Pfeifer F, Zollner A Overview of the yeast genome. Nature 1997 387 7-65. Mewes HW, Albermann K, Heumann K, Liebl S, Pfeifer F MIPS A database for protein sequences, homology data and yeast genome information. Nucleic Acid Res 1997 35 28-30. Clarke L, Baum MP Functional analysis of a centromere from fission yeast A role for centromere-specific repeated DNA sequences. Mol Cell Biol 1990 10 1863-1872. 

Having 300 000 sequences but only a few thousand structures in the databases requires a method to establish relationships of sequences to homologous proteins with known function and/or structure. 

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