Distant homology recognition using structural classification of proteins

Bateman, Alex

doi:10.1002/(sici)1097-0134(1997)1+<105::aid-prot14>3.0.co;2-s

Cited by 44 publications

(4 citation statements)

References 33 publications

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“…4,000). The strategy is to identify the folding pattern of the test protein sequence by fitting it onto a library of known structures by using pseudoenergy as a measure of fit (5,14,17,18,28,29,33,36). The library of folds is ranked in ascending order of total energy, with the lowest energy fold being taken as the most probable match.…”

Section: Methodsmentioning

confidence: 99%

Molecular Analysis of the Multiple GroEL Proteins of Chlamydiae

Karunakaran

Noguchi

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et al. 2003

J Bacteriol

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Genome sequencing revealed that all six chlamydiae genomes contain three groEL-like genes (groEL1, groEL2, and groEL3). Phylogenetic analysis of groEL1, groEL2, and groEL3 indicates that these genes are likely to have been present in chlamydiae since the beginning of the lineage. Comparison of deduced amino acid sequences of the three groEL genes with those of other organisms showed high homology only for groEL1, although comparison of critical amino acid residues that are required for polypeptide binding of the Escherichia coli chaperonin GroEL revealed substantial conservation in all three chlamydial GroELs. This was further supported by three-dimensional structural predictions. All three genes are expressed constitutively throughout the developmental cycle of Chlamydia trachomatis, although groEL1 is expressed at much higher levels than are groEL2 and groEL3. Transcription of groEL1, but not groEL2 and groEL3, was elevated when HeLa cells infected with C. trachomatis were subjected to heat shock. Western blot analysis with polyclonal antibodies raised against recombinant GroEL1, GroEL2, and GroEL3 demonstrated the presence of the three proteins in C. trachomatis elementary bodies, with GroEL1 being present in the largest amount. Only C. trachomatis groEL1 and groES together complemented a temperature-sensitive E. coli groEL mutant. Complementation did not occur with groEL2 or groEL3 alone or together with groES. The role for each of the three GroELs in the chlamydial developmental cycle and in disease pathogenesis requires further study.The group I chaperonins, such as the GroEL protein of Escherichia coli and Hsp60 of eukaryotic mitochondria and plant chloroplasts, are a ubiquitous family of abundant proteins. These proteins play an essential role in ensuring that genome encoded proteins are expressed as fully functional molecules. In E. coli, homopolymers of GroEL interact with a ring-shaped cofactor composed of septamers of GroES or Hsp10 that forms the lid on an Anfinsen protein folding cage in which polypeptide substrates are assisted in folding into the correct three-dimensional (3-D) structure (24, 39). GroEL and GroES are present in the cytoplasm of unstressed E. coli cells, and both proteins are essential for bacterial growth at all temperatures (11). GroEL expression increases during a variety of conditions such as heat shock, nutrient deprivation, infection, and inflammatory reaction and functions to stabilize cellular proteins (40). GroEL proteins are highly conserved in sequence among bacteria and are recognized in hosts by Toll-like receptors as part of an innate defense system (38). GroELs are implicated in bacterial disease pathogenesis (41), and antibodies to chlamydial GroEL have been strongly associated with chlamydial disease sequelae (4). The mechanistic explanation underlying this epidemiological correlation remains undefined. We therefore undertook detailed bioinformatic, genetic, and immunologic studies of the three chlamydial groEL genes and proteins revealed during whole genome seque...

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Section: Methodsmentioning

confidence: 99%

Molecular Analysis of the Multiple GroEL Proteins of Chlamydiae

Karunakaran

Noguchi

Read³

et al. 2003

J Bacteriol

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“…Equation 8 suggests a scoring function S, which is proportional to the negative log conditional probability that the given structure is correct, given a set of distances. (9) An advantage of using Eq. 9 instead of Eq.…”

Section: Deriving Knowledge-based Scoring Functions From the Bayesianmentioning

confidence: 99%

“…In the comparative modeling category, the methodologies rely on the presence of one or more evolutionarily related template protein structures that are used to construct a model. Traditionally, the evolutionary relationship can be deduced from sequence similarity (7)(8)(9) or by "threading" a sequence against a library of structures and selecting the best match (10,11). However, because of the improved sensitivity of the sequence similarity based methods, the threading approach has essentially been supplanted (12,13).…”

Section: Introductionmentioning

confidence: 99%

Scoring Functions for De Novo Protein Structure Prediction Revisited

Ngan

Hung²,

Liu³

et al. 2008

Protein Structure Prediction

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SummaryDe novo protein structure prediction methods attempt to predict tertiary structures from sequences based on general principles that govern protein folding energetics and/or statistical tendencies of conformational features that native structures acquire, without the use of explicit templates. A general paradigm for de novo prediction involves sampling the conformational space, guided by scoring functions and other sequence-dependent biases, such that a large set of candidate ("decoy") structures are generated, and then selecting native-like conformations from those decoys using scoring functions as well as conformer clustering. High-resolution refinement is sometimes used as a final step to fine-tune native-like structures. There are two major classes of scoring functions. Physics-based functions are based on mathematical models describing aspects of the known physics of molecular interaction. Knowledge-based functions are formed with statistical models capturing aspects of the properties of native protein conformations. We discuss the implementation and use of some of the scoring functions from these two classes for de novo structure prediction in this chapter.

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“…But, pairwise sequence alignment based search procedures are unlikely to be able to identify related proteins with low sequence similarity. However, these distantly related proteins could often be identified with the use of threedimensional (3-D) structural information (11) as the structure is conserved better than sequence during evolution (12,13) Thus, use of structural information could potentially enhance the functional assignments (14 -17). Moreover, structure prediction with relevant biochemical motifs can provide more detailed functional insights than sequence comparisons alone (18 -20).…”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Characterization of Gene Products Encoded in the Human Genome by Homology Detection

2004

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SummaryAvailability of the human genome data has enabled the exploration of a huge amount of biological information encoded in it. There are extensive ongoing experimental efforts to understand the biological functions of the gene products encoded in the human genome. However, computational analysis can aid immensely in the interpretation of biological function by associating known functional/structural domains to the human proteins. In this article we have discussed the implications of such associations. The association of structural domains to human proteins could help in prioritizing the targets for structure determination in the structural genomics initiatives. The protein kinase family is one of the most frequently occurring protein domain families in the human proteome while P-loop hydrolase, which comprises many GTPases and ATPases, is a highly represented superfamily. Using the superfamily relationships between families of unknown and known structures we could increase structural information content of the human genome by about 5%. We could also make new associations of domain families to 33 human proteins that are potentially linked to genetically inherited diseases.

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Distant homology recognition using structural classification of proteins

Cited by 44 publications

References 33 publications

Molecular Analysis of the Multiple GroEL Proteins of Chlamydiae

Molecular Analysis of the Multiple GroEL Proteins of Chlamydiae

Scoring Functions for De Novo Protein Structure Prediction Revisited

Structural and Functional Characterization of Gene Products Encoded in the Human Genome by Homology Detection

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