Chemistry of Biomacromolecules: Current Research Articles
Current Articles about the Chemistry of Biomacromolecules published in scientific online journals.
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On this page considered biochemistry journals:
BMC Structural Biology - published by
BioMed Central -
... is an open access journal publishing original peer-reviewed research articles in investigations into the structure and function of biological macromolecules.
Biomacromolecules - published by
The American Chemical Society -
... explores the interactions of macromolecules with biological systems and their environments as well as biological approaches to the design of polymeric materials. Cutting-edge research at the interface of polymer science and biological sciences.
Current research articles of the mentioned
journals:
Ricardo M. P. da Silva, Sofia G. Caridade, Julio San Román, João F. Mano, and Rui L. Reis Web Release Date: Thu, 24 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm8001649
Background:
: In search of new antifungal targets of potential interest for pharmaceutical companies, we initiated a comparative genomics study to identify the most promising protein-coding genes in fungal genomes. One criterion was the protein sequence conservation between reference pathogenic genomes. A second criterion was that the corresponding gene in Saccharomyces cerevisiae should be essential. Since thiamine pyrophosphate is an essential product involved in a variety of metabolic pathways, proteins responsible for its production satisfied these two criteria.
Results:
: We report the enzymatic characterization and the crystallographic structure of the Candida albicans Thiamine pyrophosphokinase. The protein was co-crystallized with thiamine or thiamine-PNP.
Conclusions:
: The presence of an inorganic phosphate in the crystallographic structure opposite the known AMP binding site relative to the thiamine moiety suggests that a second AMP molecule could be accommodated in the C. albicans structure. Together with the crystallographic structures of the enzyme/substrate complexes this suggests the existence of a secondary, less specific, nucleotide binding site in the Candida albicans thiamine pyrophosphokinase which could transiently serve during the release or the binding of ATP. The structures also highlight a conserved Glutamine residue (Q138) which could interact with the ATP alpha-phosphate and act as gatekeeper. Finally, the TPK/Thiamine-PNP complex is consistent with a one step mechanism of pyrophosphorylation.
Andrew K. Ekaputra, Glenn D. Prestwich, Simon M. Cool, and Dietmar W. Hutmacher Web Release Date: Wed, 23 Jul 2008 00:00:00 EDT (Communication) DOI: 10.1021/bm800565u
Jianguo Sun, Stefan V. Graeter, Lin Yu, Shifeng Duan, Joachim P. Spatz, and Jiandong Ding Web Release Date: Wed, 23 Jul 2008 00:00:00 EDT (Communication) DOI: 10.1021/bm800477s
Urate oxidase (EC 1.7.3.3) or UOX catalyzes the conversion of uric acid and molecular oxygen to 5-hydroxyisourate and hydrogen peroxide. The catalytic mechanism was investigated using a ternary complex formed between the enzyme, uric acid, and cyanide that stabilizes an intermediate state of the reaction. When uric acid is replaced by a competitive inhibitor, no complex with cyanide can be formed. The X-ray structure of this compulsory ternary complex led to a number of mechanistic evidences that support a sequential mechanism in which the two reagents, dioxygen and a water molecule, process through a common site located 3.5 A above the mean plane of the ligand. This site is built by the side chains of Asn 254, and Thr 57, two conserved residues belonging to two different subunits of the homo-tetramer. This mechanism present a number of similarities with other cofactor-less oxidases and more precisely with catalase, the enzyme that performs the reverted reaction, i.e. the conversion of hydrogen peroxide to oxygen and water.
Maria V. Lozano, Daniel Torrecilla, Dolores Torres, Anxo Vidal, Fernando Domínguez, and Maria J Alonso Web Release Date: Sat, 19 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm800298u
Tomasz M. Kapłon, Grzegorz Rymarczyk, Małgorzata Nocula-Ługowska, Michał Jakób, Marian Kochman, Marek Lisowski, Zbigniew Szewczuk, and Andrzej Ożyhar Web Release Date: Fri, 18 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm800135m
Josefina Lindqvist, Daniel Nyström, Emma Östmark, Per Antoni, Anna Carlmark, Mats Johansson, Anders Hult, and Eva Malmström Web Release Date: Fri, 18 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm800193n
Ji Sun Park, Kyeongsoon Park, Dae Gyun Woo, Han Na Yang, Hyung-Min Chung, and Keun-Hong Park Web Release Date: Thu, 17 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm800251x
Wellington S. Adriano, Dany B. Mendonça, Dasciana S. Rodrigues, Enrique J. Mammarella, and Raquel L. C. Giordano Web Release Date: Thu, 17 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm8002754
Paul M. Zelisko, Kulwinder K. Flora, John D. Brennan, and Michael A. Brook Web Release Date: Wed, 16 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm800226z
Background:
Although multiple templates are frequently used in comparative modeling, the effect of inclusion of additional template(s) on model accuracy (when compared to that of corresponding single-template based models) is not clear. To address this, we systematically analyze two-template models, the simplest case of multiple-template modeling. For an existing target-template pair (single-template modeling), a two-template based model of the target sequence is constructed by including an additional template without changing the original alignment to measure the effect of the second template on model accuracy.
Results:
Even though in a large number of cases a two-template model showed higher accuracy than the corresponding one-template model, over the entire dataset only a marginal improvement was observed on average, as there were many cases where no change or the reverse change was observed. The increase in accuracy due to the structural complementarity of the templates increases at higher alignment accuracies. The combination of templates showing the highest potential for improvement is that where both templates share similar and low (less than 30%) sequence identity with the target, as well as low sequence identity with each other. The structural similarity between the templates also helps in identifying template combinations having a higher chance of resulting in an improved model.
Conclusions:
Inclusion of additional template(s) does not necessarily improve model quality, but there are distinct combinations of the two templates, which can be selected a priori, that tend to show improvement in model quality over the single template model. The benefit derived from the structural complementarity is dependent on the accuracy of the modeling alignment. The study helps to explain the observation that a careful selection of templates together with an accurate target:template alignment are necessary to the benefit from using multiple templates in comparative modeling and provides guidelines to maximize the benefit from using multiple templates. This enables formulation of simple template selection rules to rank targets of a protein family in the context of structural genomics.
Sander S. van Leeuwen, Slavko Kralj, Gerrit J. Gerwig, Lubbert Dijkhuizen, and Johannis P. Kamerling Web Release Date: Fri, 11 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm800410w
Jeppe Madsen, Steven P. Armes, Karima Bertal, Hannah Lomas, Sheila MacNeil, and Andrew L. Lewis Web Release Date: Fri, 4 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm8005006
Alexandra Andersson Roos, Ulrica Edlund, John Sjöberg, Ann-Christine Albertsson, and Henrik Stålbrand Web Release Date: Tue, 1 Jul 2008 00:00:00 EDT (Article) DOI: 10.1021/bm701399m
Tea Indest, Janne Laine, Volker Ribitsch, Leena-Sisko Johansson, Karin Stana-Kleinschek, and Simona Strnad Web Release Date: Sat, 28 Jun 2008 00:00:00 EDT (Article) DOI: 10.1021/bm800333p
Pilar Batalla, Manuel Fuentes, Cesar Mateo, Valeria Grazu, Roberto Fernandez-Lafuente, and Jose M. Guisan Web Release Date: Wed, 18 Jun 2008 00:00:00 EDT (Article) DOI: 10.1021/bm8003594
Background:
The Ambiguous Restraints for Iterative Assignment (ARIA) approach is widely used for NMR structure determination. It is based on simultaneously calculating structures and assigning NOE through an iterative protocol. The final solution consists of a set of conformers and a list of most probable assignments for the input NOE peak list.
Results:
ARIA was extended with a series of graphical tools to facilitate a detailed analysis of the intermediate and final results of the ARIA protocol. These additional features provide (i) an interactive contact map, serving as a tool for the analysis of assignments, and (ii) graphical representations of structure quality scores and restraint statistics. The interactive contact map between residues can be clicked to obtain information about the restraints and their contributions. Profiles of quality scores are plotted along the protein sequence, and contact maps provide information of the agreement with the data on a residue pair level.
Conclusion:
The graphical tools and outputs described here significantly extend the validation and analysis possibilities of NOE assignments given by ARIA as well as the analysis of the quality of the final structure ensemble. These tools are included in the latest version of ARIA, which is available at http://aria.pasteur.fr. The Web site also contains an installation guide, a user manual and example calculations.
Background:
Recently, we reported a unique approach to preserve the activity of some proteins in the presence of the denaturing agent, Sodium Dodecyl Sulfate (SDS). This was made possible by addition of the amphipathic solvent 2,4-Methyl-2-PentaneDiol (MPD), used as protecting but also as refolding agent for these proteins. Although the persistence of the protein activity in the SDS/MPD mixture was clearly established, preservation of their structure was only speculative until now.
Results:
In this paper, a detailed X-ray study addresses the pending question. Crystals of hen egg-white lysozyme were grown for the first time in the presence of MPD and denaturing concentrations of SDS. Depending on crystallization conditions, tetragonal crystals in complex with either SDS or MPD were collected. The conformation of both structures was very similar to the native lysozyme and the obtained complexes of SDS-lysozyme and MPD-lysozyme give some insights in the interplay of protein-SDS and protein-MPD interactions.
Conclusion:
This study clearly established the preservation of the enzyme structure in a SDS/MPD mixture. It is hypothesized that high concentrations of MPD would change the properties of SDS and lower or avoid interactions between the denaturant and the protein. These structural data therefore support the hypothesis that MPD avoids disruption of the enzyme structure by SDS and can protect proteins from SDS denaturation.
Background:
Distantly related proteins adopt and retain similar structural scaffolds despite length variations that could be as much as two-fold in some protein superfamilies. In this paper, we describe an analysis of indel regions that accommodate length variations amongst related proteins. We have developed an algorithm CUSP, to examine multi-membered PASS2 superfamily alignments to identify indel regions in an automated manner. Further, we have used the method to characterize the length, structural type and biochemical features of indels in related protein domains.
Results:
CUSP, examines protein domain structural alignments to distinguish regions of conserved structure common to related proteins from structurally unconserved regions that vary in length and type of structure. On a non-redundant dataset of 353 domain superfamily alignments from PASS2, we find that 'length- deviant' protein superfamilies show > 30% length variation from their average domain length. 60% of additional lengths that occur in indels are short-length structures (< 5 residues) while 6% of indels are > 15 residues in length. Structural types in indels also show class-specific trends.
Conclusion:
The extent of length variation varies across different superfamilies and indels show class-specific trends for preferred lengths and structural types. Such indels of different lengths even within a single protein domain superfamily could have structural and functional consequences that drive their selection, underlying their importance in similarity detection and computational modelling. The availability of systematic algorithms, like CUSP, should enable decision making in a domain superfamily-specific manner.
Background:
The structural stability of peptides in solution strongly affects their binding affinities and specificities. Thus, in peptide biotechnology, an increase in the structural stability is often desirable. The present work combines two orthogonal computational techniques, Molecular Dynamics and a knowledge-based potential, for the prediction of structural stability of short peptides (< 20 residues) in solution.
Results:
We tested the new approach on four families of short β-hairpin peptides: TrpZip, MBH, bhpW and EPO, whose structural stabilities have been experimentally measured in previous studies. For all four families, both computational techniques show considerable correlation (r > 0.65) with the experimentally measured stabilities. The consensus of the two techniques shows higher correlation (r > 0.82).
Conclusion:
Our results suggest a prediction scheme that can be used to estimate the relative structural stability within a peptide family. We discuss the applicability of this predictive approach for in-silico screening of combinatorial peptide libraries.
Background:
Ubiquitin (E3) ligases interact with specific ubiquitin conjugating (E2) enzymes to ubiquitinate particular substrate proteins. As the combination of E2 and E3 dictates the type and biological consequence of ubiquitination, it is important to understand the basis of specificity in E2:E3 interactions. The E3 ligase CHIP interacts with Hsp70 and Hsp90 and ubiquitinates client proteins that are chaperoned by these heat shock proteins. CHIP interacts with two types of E2 enzymes, UbcH5 and Ubc13-Uev1a. It is unclear, however, why CHIP binds these E2 enzymes rather than others, and whether CHIP interacts preferentially with UbcH5 or Ubc13-Uev1a, which form different types of polyubiquitin chains.
Results:
The 2.9 Å crystal structure of the CHIP U-box domain complexed with UbcH5a shows that CHIP binds to UbcH5 and Ubc13 through similar specificity determinants, including a key S-P-A motif on the E2 enzymes. The determinants make different relative contributions to the overall interactions between CHIP and the two E2 enzymes. CHIP undergoes auto-ubiquitination by UbcH5 but not by Ubc13-Uev1a. Instead, CHIP drives the formation of unanchored polyubiquitin by Ubc13-Uev1a. CHIP also interacts productively with the class III E2 enzyme Ube2e2, in which the UbcH5- and Ubc13-binding specificity determinants are highly conserved.
Conclusion:
The CHIP:UbcH5a structure emphasizes the importance of specificity determinants located on the long loops and central helix of the CHIP U-box, and on the N-terminal helix and loops L4 and L7 of its cognate E2 enzymes. The S-P-A motif and other specificity determinants define the set of cognate E2 enzymes for CHIP, which likely includes several Class III E2 enzymes. CHIP's interactions with UbcH5, Ube2e2 and Ubc13-Uev1a are consistent with the notion that Ubc13-Uev1a may work sequentially with other E2 enzymes to carry out K63-linked polyubiquitination of CHIP substrates.
Background:
Circular dichroism spectroscopy is a widely used technique to analyze the secondary structure of proteins in solution. Predictive methods use the circular dichroism spectra from proteins of known tertiary structure to assess the secondary structure contents of a protein with unknown structure given its circular dichroism spectrum.
Results:
We developed K2D2, a method with an associated web server to estimate protein secondary structure from circular dichroism spectra. The method uses a self-organized map of spectra from proteins with known structure to deduce a map of protein secondary structure that is used to do the predictions.
Conclusion:
The K2D2 server is publicly accessible at http://www.ogic.ca/projects/k2d2/. It accepts as input a circular dichroism spectrum and outputs the estimated secondary structure content (alpha-helix and beta-strand) of the corresponding protein, as well as an estimated measure of error.
Background:
Comparative modeling is a technique to predict the three dimensional structure of a given protein sequence based primarily on its alignment to one or more proteins with experimentally determined structures. A major bottleneck of current comparative modeling methods is the lack of methods to accurately refine a starting initial model so that it approaches the resolution of the corresponding experimental structure. We investigate the effectiveness of a graph-theoretic clique finding approach to solve this problem.
Results:
Our method takes into account the information presented in multiple templates/alignments at the three-dimensional level by mixing and matching regions between different initial comparative models. This method enables us to obtain an optimized conformation ensemble representing the best combination of secondary structures, resulting in the refined models of higher quality. In addition, the process of mixing and matching accumulates near-native conformations, resulting in discriminating the native-like conformation in a more effective manner. In the seventh Critical Assessment of Structure Prediction (CASP7) experiment, the refined models produced are more accurate than the starting initial models.
Conclusion:
This novel approach can be applied without any manual intervention to improve the quality of comparative predictions where multiple template/alignment combinations are available for modeling, producing conformational models of higher quality than the starting initial predictions.
