BMC Structural Biology最新文献

{"title":"Erratum to: Prediction and analysis of the modular structure of cytochrome P450 monooxygenases","authors":"Demet Sirim, Michael Widmann, Florian Wagner, Jürgen Pleiss","doi":"10.1186/1472-6807-12-4","DOIUrl":"https://doi.org/10.1186/1472-6807-12-4","url":null,"abstract":"","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4955056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A transcriptional-switch model for Slr1738-controlled gene expression in the cyanobacterium Synechocystis","authors":"Paul Garcin,&nbsp;Olivier Delalande,&nbsp;Ju-Yuan Zhang,&nbsp;Corinne Cassier-Chauvat,&nbsp;Franck Chauvat,&nbsp;Yves Boulard","doi":"10.1186/1472-6807-12-1","DOIUrl":"https://doi.org/10.1186/1472-6807-12-1","url":null,"abstract":"<p>Protein-DNA interactions play a crucial role in the life of biological organisms in controlling transcription, regulation, as well as DNA recombination and repair. The deep understanding of these processes, which requires the atomic description of the interactions occurring between the proteins and their DNA partners is often limited by the absence of a 3D structure of such complexes.</p><p>In this study, using a method combining sequence homology, structural analogy modeling and biochemical data, we first build the 3D structure of the complex between the poorly-characterized PerR-like regulator Slr1738 and its target DNA, which controls the defences against metal and oxidative stresses in <i>Synechocystis</i>. In a second step, we propose an expanded version of the Slr1738-DNA structure, which accommodates the DNA binding of Slr1738 multimers, a feature likely operating in the complex Slr1738-mediated regulation of stress responses. Finally, in agreement with experimental data we present a 3D-structure of the Slr1738-DNA complex resulting from the binding of multimers of the FUR-like regulator onto its target DNA that possesses internal repeats.</p><p>Using a combination of different types of data, we build and validate a relevant model of the tridimensional structure of a biologically important protein-DNA complex. Then, based on published observations, we propose more elaborated multimeric models that may be biologically important to understand molecular mechanisms.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4008142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural adaptation of extreme halophilic proteins through decrease of conserved hydrophobic contact surface","authors":"Alessandro Siglioccolo,&nbsp;Alessandro Paiardini,&nbsp;Maria Piscitelli,&nbsp;Stefano Pascarella","doi":"10.1186/1472-6807-11-50","DOIUrl":"https://doi.org/10.1186/1472-6807-11-50","url":null,"abstract":"<p>Halophiles are extremophilic microorganisms growing optimally at high salt concentrations. There are two strategies used by halophiles to maintain proper osmotic pressure in their cytoplasm: accumulation of molar concentrations of potassium and chloride with extensive adaptation of the intracellular macromolecules (\"salt-in\" strategy) or biosynthesis and/or accumulation of organic osmotic solutes (\"osmolyte\" strategy). Our work was aimed at contributing to the understanding of the shared molecular mechanisms of protein haloadaptation through a detailed and systematic comparison of a sample of several three-dimensional structures of halophilic and non-halophilic proteins. Structural differences observed between the \"salt-in\" and the mesophilic homologous proteins were contrasted to those observed between the \"osmolyte\" and mesophilic pairs.</p><p>The results suggest that haloadaptation strategy in the presence of molar salt concentration, but not of osmolytes, necessitates a weakening of the hydrophobic interactions, in particular at the level of conserved hydrophobic contacts. Weakening of these interactions counterbalances their strengthening by the presence of salts in solution and may help the structure preventing aggregation and/or loss of function in hypersaline environments.</p><p>Considering the significant increase of biotechnology applications of halophiles, the understanding of halophilicity can provide the theoretical basis for the engineering of proteins of great interest because stable at concentrations of salts that cause the denaturation or aggregation of the majority of macromolecules.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-50","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4850014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Docking studies on novel analogues of 8 methoxy fluoroquinolones against GyrA mutants of Mycobacterium tuberculosis","authors":"RS Anand,&nbsp;Sulochana Somasundaram,&nbsp;Mukesh Doble,&nbsp;CN Paramasivan","doi":"10.1186/1472-6807-11-47","DOIUrl":"https://doi.org/10.1186/1472-6807-11-47","url":null,"abstract":"<p>Fluoroquinolone resistance is a serious threat in the battle against the treatment of multi drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Fluoroquinolone resistant isolates from India had shown to have evolved several mutants in the quinolone resistance determining region (QRDR) of DNA gyrase A subunit (GyrA), the target of fluoroquinolone. In view of high prevalence of mutations in the 'hot spot' region, a study on combinatorial drug design was carried out to identify better analogues for the treatment of MDR-TB. The <i>gyrA</i> subunit 'hot spot' region of codons 90, 94 and 95 were modeled into their corresponding protein folds and used as receptors for the docking studies. Further, invitro tests were carried using the parent compounds, namely gatifloxacin and moxifloxacin and correlated with the obtained docking scores.</p><p>Molecular docking and <i>in vitro</i> studies correlated well in demonstrating the enhanced activity of moxifloxacin, when compared to gatifloxacin, on ofloxacin sensitive and resistant strains comprising of clinical isolates of MDR-TB. The evolved lead structures targeting against mutant QRDR receptors were guanosine and cholesteryl esters of gatifloxacin and moxifloxacin. They showed consistently high binding affinity values of -10.3 and -10.1 kcal/mol respectively with the target receptors. Of these, the guanosine ester showed highest binding affinity score and its log P value lied within the Lipinski's range indicating that it could have better absorptivity when it is orally administered thereby having an enhanced activity against MTB.</p><p>The docking results showed that the addition of the cholesteryl and guanosine esters to the 'DNA gyrase binding' region of gatifloxacin and moxifloxacin enhanced the binding affinity of these parent molecules with the mutant DNA gyrase receptors. Viewing the positive correlation for the docking and in vitro results with the parent compounds, these lead structures could be further evaluated for their <i>in vitro</i> and <i>in vivo</i> activity against MDR-TB.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-47","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4485930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The redundancy of NMR restraints can be used to accelerate the unfolding behavior of an SH3 domain during molecular dynamics simulations","authors":"Nathalie Duclert-Savatier,&nbsp;Leandro Martínez,&nbsp;Michael Nilges,&nbsp;Thérèse E Malliavin","doi":"10.1186/1472-6807-11-46","DOIUrl":"https://doi.org/10.1186/1472-6807-11-46","url":null,"abstract":"","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-46","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4945342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarks for flexible and rigid transcription factor-DNA docking","authors":"RyangGuk Kim,&nbsp;Rosario I Corona,&nbsp;Bo Hong,&nbsp;Jun-tao Guo","doi":"10.1186/1472-6807-11-45","DOIUrl":"https://doi.org/10.1186/1472-6807-11-45","url":null,"abstract":"<p>Structural insight from transcription factor-DNA (TF-DNA) complexes is of paramount importance to our understanding of the affinity and specificity of TF-DNA interaction, and to the development of structure-based prediction of TF binding sites. Yet the majority of the TF-DNA complexes remain unsolved despite the considerable experimental efforts being made. Computational docking represents a promising alternative to bridge the gap. To facilitate the study of TF-DNA docking, carefully designed benchmarks are needed for performance evaluation and identification of the strengths and weaknesses of docking algorithms.</p><p>We constructed two benchmarks for flexible and rigid TF-DNA docking respectively using a unified non-redundant set of 38 test cases. The test cases encompass diverse fold families and are classified into easy and hard groups with respect to the degrees of difficulty in TF-DNA docking. The major parameters used to classify expected docking difficulty in flexible docking are the conformational differences between bound and unbound TFs and the interaction strength between TFs and DNA. For rigid docking in which the starting structure is a bound TF conformation, only interaction strength is considered.</p><p>We believe these benchmarks are important for the development of better interaction potentials and TF-DNA docking algorithms, which bears important implications to structure-based prediction of transcription factor binding sites and drug design.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-45","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4049062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational analysis of a novel mutation in ETFDH gene highlights its long-range effects on the FAD-binding motif","authors":"Tze-Kiong Er,&nbsp;Chih-Chieh Chen,&nbsp;Yen-Yi Liu,&nbsp;Hui-Chiu Chang,&nbsp;Yin-Hsiu Chien,&nbsp;Jan-Gowth Chang,&nbsp;Jenn-Kang Hwang,&nbsp;Yuh-Jyh Jong","doi":"10.1186/1472-6807-11-43","DOIUrl":"https://doi.org/10.1186/1472-6807-11-43","url":null,"abstract":"<p>Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is an autosomal recessive disease caused by the defects in the mitochondrial electron transfer system and the metabolism of fatty acids. Recently, mutations in electron transfer flavoprotein dehydrogenase (<i>ETFDH</i>) gene, encoding electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) have been reported to be the major causes of riboflavin-responsive MADD. To date, no studies have been performed to explore the functional impact of these mutations or their mechanism of disrupting enzyme activity.</p><p>High resolution melting (HRM) analysis and sequencing of the entire <i>ETFDH</i> gene revealed a novel mutation (p.Phe128Ser) and the hotspot mutation (p.Ala84Thr) from a patient with MADD. According to the predicted 3D structure of ETF:QO, the two mutations are located within the flavin adenine dinucleotide (FAD) binding domain; however, the two residues do not have direct interactions with the FAD ligand. Using molecular dynamics (MD) simulations and normal mode analysis (NMA), we found that the p.Ala84Thr and p.Phe128Ser mutations are most likely to alter the protein structure near the FAD binding site as well as disrupt the stability of the FAD binding required for the activation of ETF:QO. Intriguingly, NMA revealed that several reported disease-causing mutations in the ETF:QO protein show highly correlated motions with the FAD-binding site.</p><p>Based on the present findings, we conclude that the changes made to the amino acids in ETF:QO are likely to influence the FAD-binding stability.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-43","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4837073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydration studies on the archaeal protein Sso7d using NMR measurements and MD simulations","authors":"Andrea Bernini,&nbsp;Ottavia Spiga,&nbsp;Roberto Consonni,&nbsp;Ivana Arosio,&nbsp;Paola Fusi,&nbsp;Simone Cirri,&nbsp;Annamaria Guagliardi,&nbsp;Neri Niccolai","doi":"10.1186/1472-6807-11-44","DOIUrl":"https://doi.org/10.1186/1472-6807-11-44","url":null,"abstract":"<p>How proteins approach surrounding molecules is fundamental to our understanding of the specific interactions that occur at the surface of proteins. The enhanced surface accessibility of small molecules such as organic solvents and paramagnetic probes to protein binding sites has been observed; however, the molecular basis of this finding has not been fully established. Recently, it has been suggested that hydration dynamics play a predominant role in controlling the distribution of hot spots on surface of proteins.</p><p>In the present study, the hydration of the archaeal multifunctional protein Sso7d from <i>Solfolobus solfataricus</i> was investigated using a combination of computational and experimental data derived from molecular dynamics simulations and ePHOGSY NMR spectroscopy.</p><p>We obtained a convergent protein hydration landscape that indicated how the shape and stability of the Sso7d hydration shell could modulate the function of the protein. The DNA binding domain overlaps with the protein region involved in chaperon activity and this domain is hydrated only in a very small central region. This localized hydration seems to favor intermolecular approaches from a large variety of ligands. Conversely, high water density was found in surface regions of the protein where the ATP binding site is located, suggesting that surface water molecules play a role in protecting the protein from unspecific interactions.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-44","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4837178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative void-volume analysis of psychrophilic and mesophilic enzymes: Structural bioinformatics of psychrophilic enzymes reveals sources of core flexibility","authors":"Diana I Paredes,&nbsp;Kyle Watters,&nbsp;Derek J Pitman,&nbsp;Christopher Bystroff,&nbsp;Jonathan S Dordick","doi":"10.1186/1472-6807-11-42","DOIUrl":"https://doi.org/10.1186/1472-6807-11-42","url":null,"abstract":"<p>Psychrophiles, cold-adapted organisms, have adapted to live at low temperatures by using a variety of mechanisms. Their enzymes are active at cold temperatures by being structurally more flexible than mesophilic enzymes. Even though, there are some indications of the possible structural mechanisms by which psychrophilic enzymes are catalytic active at cold temperatures, there is not a generalized structural property common to all psychrophilic enzymes.</p><p>We examine twenty homologous enzyme pairs from psychrophiles and mesophiles to investigate flexibility as a key characteristic for cold adaptation. B-factors in protein X-ray structures are one way to measure flexibility. Comparing psychrophilic to mesophilic protein B-factors reveals that psychrophilic enzymes are more flexible in 5-turn and strand secondary structures. Enzyme cavities, identified using CASTp at various probe sizes, indicate that psychrophilic enzymes have larger average cavity sizes at probe radii of 1.4-1.5 ?, sufficient for water molecules. Furthermore, amino acid side chains lining these cavities show an increased frequency of acidic groups in psychrophilic enzymes.</p><p>These findings suggest that embedded water molecules may play a significant role in cavity flexibility, and therefore, overall protein flexibility. Thus, our results point to the important role enzyme flexibility plays in adaptation to cold environments.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-42","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4807493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central domain deletions affect the SAXS solution structure and function of Yeast Hsp40 proteins Sis1 and Ydj1","authors":"Julio C Silva,&nbsp;Julio C Borges,&nbsp;Douglas M Cyr,&nbsp;Carlos HI Ramos,&nbsp;Iris L Torriani","doi":"10.1186/1472-6807-11-40","DOIUrl":"https://doi.org/10.1186/1472-6807-11-40","url":null,"abstract":"<p>Ydj1 and Sis1 are structurally and functionally distinct Hsp40 proteins of the yeast cytosol. S<i>is1</i> is an essential gene whereas the <i>ydj1</i> gene is essential for growth at elevated temperatures and cannot complement <i>sis1</i> gene deletion. Truncated polypeptides capable of complementing the <i>sis1</i> gene deletion comprise the J-domain of either Sis1 or Ydj1 connected to the G/F region of Sis1 (but not Ydj1). Sis1 mutants in which the G/F was deleted but G/M maintained were capable of complementing the <i>sis1</i> gene deletion.</p><p>To investigate the relevance of central domains on the structure and function of Ydj1 and Sis1 we prepared Sis1 constructs deleting specific domains. The mutants had decreased affinity for heated luciferase but were equally capable of stimulating ATPase activity of Hsp70. Detailed low resolution structures were obtained and the overall flexibility of Hsp40 and its mutants were assessed using SAXS methods. Deletion of either the G/M or the G/M plus CTDI domains had little impact on the quaternary structure of Sis1 analyzed by the SAXS technique. However, deletion of the ZFLR-CTDI changed the relative position of the J-domains in Ydj1 in such a way that they ended up resembling that of Sis1. The results revealed that the G/F and G/M regions are not the only flexible domains. All model structures exhibit a common clamp-like conformation.</p><p>Our results suggest that the central domains, previously appointed as important features for substrate binding, are also relevant keeping the J-domains in their specific relative positions. The clamp-like architecture observed seems also to be favorable to the interactions of Hsp40 with Hsp70.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-40","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4768842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}