A platform for integrating threading results with protein
  family analyses

Pazos, Florencio; Rost, Burkhard; Valencia, Alfonso

doi:10.1093/bioinformatics/15.12.1062

Cited by 11 publications

(4 citation statements)

References 15 publications

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“…We evaluated in detail the distribution of the conserved, apolar, tree‐determinant, and correlated residues that were calculated from the sequences of the PsbO protein family. The visualization of the sequence characteristics in the various models and the numerical evaluation of the significance of their distribution (see Methods section) was carried out with the program Threadlize 31…”

Section: Resultsmentioning

confidence: 99%

Threading structural model of the manganese‐stabilizing protein PsbO reveals presence of two possible β‐sandwich domains

et al. 2001

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The manganese-stabilizing protein (PsbO) is an essential component of photosystem II (PSII) and is present in all oxyphotosynthetic organisms. PsbO allows correct water splitting and oxygen evolution by stabilizing the reactions driven by the manganese cluster. Despite its important role, its structure and detailed functional mechanism are still unknown. In this article we propose a structural model based on fold recognition and molecular modeling. This model has additional support from a study of the distribution of characteristics of the PsbO sequence family, such as the distribution of conserved, apolar, tree-determinants, and correlated positions. Our threading results consistently showed PsbO as an all-beta (beta) protein, with two homologous beta domains of approximately 120 amino acids linked by a flexible Proline-Glycine-Glycine (PGG) motif. These features are compatible with a general elongated and flexible architecture, in which the two domains form a sandwich-type structure with Greek key topology. The first domain is predicted to include 8 to 9 beta-strands, the second domain 6 to 7 beta-strands. An Ig-like beta-sandwich structure was selected as a template to build the 3-D model. The second domain has, between the strands, long-loops rich in Pro and Gly that are difficult to model. One of these long loops includes a highly conserved region (between P148 and P174) and a short alpha-helix (between E181 and N188)). These regions are characteristic parts of PsbO and show that the second domain is not so similar to the template. Overall, the model was able to account for much of the experimental data reported by several authors, and it would allow the detection of key residues and regions that are proposed in this article as essential for the structure and function of PsbO.

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Section: Resultsmentioning

confidence: 99%

Threading structural model of the manganese‐stabilizing protein PsbO reveals presence of two possible β‐sandwich domains

et al. 2001

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“…The models were evaluated with a set of tools based on the evaluation of some characteristics of the model: fold compactness, distribution of apolar residues, family and subfamily conserved residues (tree determinants) and correlated mutations (Pazos et al , 1997a; Olmea et al , 1999). The analysis of this information and the visual inspection of the corresponding models was carried out with the THREADLIZE package (Pazos et al , 1999; http://www.cnb. uam.es/~pazos/threadlize).…”

Section: Methodsmentioning

confidence: 99%

Deciphering the action of aromatic effectors on the prokaryotic enhancer‐binding protein XylR: a structural model of its N‐terminal domain

Devos

Garmendia

Valencia

2002

Environmental Microbiology

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The prokaryotic enhancer-binding protein XylR is the central regulator of the toluene degradation pathway in Pseudomonas species. Copious genetic and biochemical data indicate that the N-terminal domain of the protein (domain A) interacts directly with m-xylene, which renders the protein competent as a transcriptional activator. Single-site and shuffling mutants of XylR or homologues have been reported to change or expand their effector profiles. Here, we follow a fold recognition approach to generate three-dimensional models of the domain A of XylR and DmpR with the purpose of deciphering the molecular activity of this protein family. The model is based on the crystallographic data of the rat catechol O-methyltransferase, a typical alpha/beta fold, consisting of eight alpha-helices and seven beta-strands. The fold identification is supported by physico-chemical properties of conserved amino acids, distribution of residues characteristic of the sequence families and confrontation with experimental data. The model not only provides a rationale for understanding published experimental data, but also suggests the molecular mechanism of the activation step and is a potentially useful conceptual tool for designing regulators with predefined inducer specificities.

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“…First, a set of candidate folds was chosen based not only on the scores of the three best hits proposed by each threading program, but also on the fold similarity among the three best hits according to the FSSP database [54]. Then, 1D and 3D alignments of the query protein with each of the hit templates were inspected using the THREADLIZE package [55]. In addition, CLUSTALX [56] was used to align the PsbQ sequence, and the profiles of the proposed structures derived from the alignments were deposited in the HSSP database [57].…”

Section: Bioinformatics Methodsmentioning

confidence: 99%

“…In order to select the best template to construct a remote 3D model for the C-terminal domain (residues 46-149) of PsbQ, the structural alignments between the problem PsbQ protein and each of the threading hits (Tables 1 and 2) were manually inspected using the THREADLIZE package [55], bearing in mind the compatibility of the predicted [37] and known secondary structures. Also, the quality of the sequence alignment between the families (each threading hit family obtained from HSSP database), the number and distribution of gaps, the sequence homology and the hydropathy profile were analysed.…”

Section: Selection Of the Best Pdb Template For The C-terminal Domainmentioning

confidence: 99%

The single tryptophan of the PsbQ protein of photosystem II is at the end of a 4‐α‐helical bundle domain

Balsera

Arellano

Pazos

et al. 2003

European Journal of Biochemistry

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We examined the microenvironment of the single tryptophan and the tyrosine residues of PsbQ, one of the three main extrinsic proteins of green algal and higher plant photosystem II. On the basis of this information and the previous data on secondary structure [Balsera, M., Arellano, J.B., Gutie´rrez, J.R., Heredia, P., Revuelta, J.L. & De Las Rivas, J. (2003) Biochemistry 42, 1000-1007], we screened structural models derived by combining various threading approaches. Experimental results showed that the tryptophan residue is partially buried in the core of the protein but still in a polar environment, according to the intrinsic fluorescence emission of PsbQ and the fact that fluorescence quenching by iodide was weaker than that by acrylamide. Furthermore, quenching by cesium suggested that a positively charged barrier shields the tryptophan microenvironment. Comparison of the absorption spectra in native and denaturing conditions indicated that one or two out of six tyrosines of PsbQ are buried in the core of the structure. Using threading methods, a 3D structural model was built for the C-terminal domain of the PsbQ protein family (residues 46-149), while the N-terminal domain is predicted to have a flexible structure. The model for the C-terminal domain is based on the 3D structure of cytochrome b 562 , a mainly a-protein with a helical up/down bundle folding. Despite the large sequence differences between the template and PsbQ, the structural and energetic parameters for the explicit model are acceptable, as judged by the corresponding tools. This 3D model is compatible with the experimentally determined environment of the tryptophan residue and with published structural information. The future experimental determination of the 3D structure of the protein will offer a good validation point for our model and the technology used. Until then, the model can provide a starting point for further studies on the function of PsbQ.

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A platform for integrating threading results with protein family analyses

Abstract: We have developed a package for the interactive visualization of results from different threading programs. Additionally, we have integrated relevant information about protein sequence, function, evolution, and structure into the interface.

Cited by 11 publications

References 15 publications

Threading structural model of the manganese‐stabilizing protein PsbO reveals presence of two possible β‐sandwich domains

Threading structural model of the manganese‐stabilizing protein PsbO reveals presence of two possible β‐sandwich domains

Deciphering the action of aromatic effectors on the prokaryotic enhancer‐binding protein XylR: a structural model of its N‐terminal domain

The single tryptophan of the PsbQ protein of photosystem II is at the end of a 4‐α‐helical bundle domain

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