Proteins domain families

Sonnhammer, E.L., Eddy, S.R., Durbin, R. Pfam a comprehensive database of protein domain families based on seed alignments. Proteins 28 405-420, 1997. 

Prosite (http //www.expasy.org/prosite), database of protein domains, families, and functional sites. 

Prosite is perhaps the best known of the domain databases (Hofmann et al., 1999). The Prosite database is a good source of high quality annotation for protein domain families. Prosite documentation includes a section on the functional meaning of a match to the entry and a list of example members of the family. Prosite documentation also includes literature references and cross links to other databases such as the PDB collection of protein structures (Bernstein et al., 1977). For each Prosite document, there is a Prosite pattern, profile, or both to detect the domain family. The profiles are the most sensitive detection method in Prosite. The Prosite profiles provide Zscores for matches allowing statistical evaluation of the match to a new protein. Profiles are now available for many of the common protein domains. Prosite profiles use the generalized profile software (Bucher et al., 1996). 

Pfam (Comprehensive Collection of Protein Domain Families)... 

Intercellular protein interactions —> a complete characterization of one protein domain family. 

Identify the ProSite residues and protein domain families for the following proteins of given amino acid sequences ... 

Many databases provide information on functional annotation of the genomes of organisms. One such high-quality standard database is Pfam (19). Pfam is fundamentally a protein domain family database derived based on sequence similarity. Pfam provides details on the functional properties of protein domains of known function. Out of 1,590, 1,495, and 1,536 proteins encoded in the genomes of 26695, J99, and HPAG1 strains of H. pylori, respectively, 1,113, 1,130, and 1,143 proteins have at least 1 protein domain associated (defined by Pfam) with the amino acid sequence. Therefore, for these domains of H. pylori proteins, preliminary indication of their functions is available. 

All such cases with novel domain family assignments are characterized by poor sequence identity and therefore may not be interpreted as bona fide members of the protein domain families concerned. They may be interpreted as remotely related to the family concerned, and hence functional similarity between such H. pylori protein sequences with members of the family concerned may or may not exist. 

Highly populated protein domain families of H. pylori include (1) the cellular component Helicobacter outer membrane protein family (2) the sell family, which is associated with P-lactamase activity (3) members of the CagA and VacA protein families, which are secreted into host cells and are involved in pathogenesis (4) the ABC transporter family, which is associated with ATP-dependent transport of molecules across the membrane (5) the DNA methyltransferase protein domain family (6) the radical SAM (S-adenosylmethionine) family associated with various metabolic functions of pathogens and (7) the response regulator receiver domain family, which is involved in receiving the signal from the sensor domain in bacterial two-component systems. 

Newly discovered evolutionary relationships involving protein domain families for which no bona fide member is currently known to be present in H. pylori are discussed in the following section. According to the present analysis, however, specific H. pylori proteins are shown to be related to these families. 

Members from the KorB domain family are characterized by the DNA-binding helix-turn-helix motif (a-3 and a-4). Examples of this protein domain family include the well-studied DNA-binding KorB domain protein, the three-dimensional structure of which has been solved with its operator (PDB accession code lr71, DNA/RNA-binding 3-helical bundle fold Fig. 2a). Amino acid residues outside the HTH motif (Thr-211 and Arg-240) determine the sequence-specific DNA binding (35) (Fig. 2a). 

A number of relationships have been identified involving hypothetical H. pylori proteins and protein domain families for which bona fide members are present in H. pylori. 

PTPS (6-Pyruvoyl Tetmhydropterin Synthase). 6-Pyruvoyl tetrahy-dropterin synthase catalyzes formation of tetrahydrobiopterin biosynthesis. Tetrahydrobiopterin is a cofactor for several important enzymes, such as aromatic amino acid hydroxylases and nitric oxide synthase (57). H. pylori protein HPAG1 0913 shares homology with members of the protein domain family PTPS. H. pylori protein shares poor sequence identity of 14% with the PTPS profile at an E-value of 10 10 and covers about 95% of the length of the profile. Fold recognition results also confirm the relationship between H. pylori protein and the PTPS protein domain family. A fold recognition algorithm ensures fitness of the H. pylori protein sequence on the three-dimensional structure of PTPS from... 

Gowri VS, Krishnadev O, Swamy CS et al (2006) MulPSSM a database of multiple position-specific scoring matrices of protein domain families. Nucleic Acids Res 34 D243-D246... 

Corpet, F Gouzy, J. Kahn, D. (1999). Recent improvements of the ProDom database of protein domain families. Nucleic Acids Res 27, 263-7. 

ProDom [20,21] is a collection of protein domain families automatically derived from the Swiss-Prot and TrEMBL databases using a novel approach based on recursive PSI-BLAST searches. 

A comprehensive description of the databases and methods for domain, family, and pattern identification is available in chapter 2. Therefore, in this chapter, the discussion of the application of family and domain information to function assignment will be limited to Pfam, the virtual standard in protein domain/family classification, and to InterPro and CDD, two resources that integrate multiple domain databases. In addition, I discuss tools that can be used to scan those databases, namely HMMER,... 

ProDom Protein domain families http //www.toulouse.inra.fr/prodom. html... 

Dessailly, B. H., Nair, R., Jaroszewski, L., et al. 2009. PSI-2 Structural genomics to cover protein domain family space. Structure 17 869-881. 

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