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91.
Bertini I Felli IC Gonnelli L Pierattelli R Spyranti Z Spyroulias GA 《Journal of biomolecular NMR》2006,36(2):111-122
The copper-mediated protein–protein interaction between yeast Atx1 and Ccc2 has been examined by protonless heteronuclear NMR and compared with the already available 1H–15N HSQC information. The observed chemical shift variations are analyzed with respect to the actual solution structure, available
through intermolecular NOEs. The advantage of using the CON-IPAP spectrum with respect to the 1H–15N HSQC resides in the increased number of signals observed, including those of prolines. CBCACO-IPAP experiments allow us
to focus on the interaction region and on side-chain carbonyls, while a newly designed CEN-IPAP experiment on side-chains
of lysines. An attempt is made to rationalize the chemical shift variations on the basis of the structural data involving
the interface between the proteins and the nearby regions. It is here proposed that protonless
13C direct-detection NMR is a useful complement to 1H based NMR spectroscopy for monitoring protein–protein and protein–ligand interactions.
Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at 相似文献
92.
Canales-Mayordomo A Fayos R Angulo J Ojeda R Martín-Pastor M Nieto PM Martín-Lomas M Lozano R Giménez-Gallego G Jiménez-Barbero J 《Journal of biomolecular NMR》2006,35(4):225-239
The binding site and backbone dynamics of a bioactive complex formed by the acidic fibroblast growth factor (FGF-1) and a specifically designed heparin hexasaccharide has been investigated by HSQC and relaxation NMR methods. The comparison of the relaxation data for the free and bound states has allowed showing that the complex is monomeric, and still induces mutagenesis, and that the protein backbone presents reduced motion in different timescale in its bound state, except in certain points that are involved in the interaction with the fibroblast growth factor receptor (FGFR).Angeles Canales-Mayordomo and Rosa Fayos have contributed equally to this research. 相似文献
93.
Jiancong Xu Michael F. Crowley Jeremy C. Smith 《Protein science : a publication of the Protein Society》2009,18(5):949-959
The organization and assembly of the cellulosome, an extracellular multienzyme complex produced by anaerobic bacteria, is mediated by the high‐affinity interaction of cohesin domains from scaffolding proteins with dockerins of cellulosomal enzymes. We have performed molecular dynamics simulations and free energy calculations on both the wild type (WT) and D39N mutant of the C. thermocellum Type I cohesin‐dockerin complex in aqueous solution. The D39N mutation has been experimentally demonstrated to disrupt cohesin‐dockerin binding. The present MD simulations indicate that the substitution triggers significant protein flexibility and causes a major change of the hydrogen‐bonding network in the recognition strips—the conserved loop regions previously proposed to be involved in binding—through electrostatic and salt‐bridge interactions between β‐strands 3 and 5 of the cohesin and α‐helix 3 of the dockerin. The mutation‐induced subtle disturbance in the local hydrogen‐bond network is accompanied by conformational rearrangements of the protein side chains and bound water molecules. Additional free energy perturbation calculations of the D39N mutation provide differences in the cohesin‐dockerin binding energy, thus offering a direct, quantitative comparison with experiments. The underlying molecular mechanism of cohesin‐dockerin complexation is further investigated through the free energy profile, that is, potential of mean force (PMF) calculations of WT cohesin‐dockerin complex. The PMF shows a high‐free energy barrier against the dissociation and reveals a stepwise pattern involving both the central β‐sheet interface and its adjacent solvent‐exposed loop/turn regions clustered at both ends of the β‐barrel structure. 相似文献
94.
Yiren Xu Carlos D. Amero Dileep K. Pulukkunat Venkat Gopalan Mark P. Foster 《Journal of molecular biology》2009,393(5):1043-935
Ribonuclease P (RNase P) is a ribonucleoprotein (RNP) enzyme that catalyzes the Mg2+-dependent 5′ maturation of precursor tRNAs. In all domains of life, it is a ribozyme: the RNase P RNA (RPR) component has been demonstrated to be responsible for catalysis. However, the number of RNase P protein subunits (RPPs) varies from 1 in bacteria to 9 or 10 in eukarya. The archaeal RPR is associated with at least 4 RPPs, which function in pairs (RPP21-RPP29 and RPP30-POP5). We used solution NMR spectroscopy to determine the three-dimensional structure of the protein-protein complex comprising Pyrococcus furiosus RPP21 and RPP29. We found that the protein-protein interaction is characterized by coupled folding of secondary structural elements that participate in interface formation. In addition to detailing the intermolecular contacts that stabilize this 30-kDa binary complex, the structure identifies surfaces rich in conserved basic residues likely vital for recognition of the RPR and/or precursor tRNA. Furthermore, enzymatic footprinting experiments allowed us to localize the RPP21-RPP29 complex to the specificity domain of the RPR. These findings provide valuable new insights into mechanisms of RNP assembly and serve as important steps towards a three-dimensional model of this ancient RNP enzyme. 相似文献
95.
Stanley Tam Haiyuan Yu Kavitha Venkatesan Danny Mou Venus Swearingen Muhammed A Yildirim Han Yan Amélie Dricot David Szeto Chenwei Lin Tong Hao Changyu Fan Stuart Milstein Denis Dupuy Robert Brasseur David E Hill Michael E Cusick Marc Vidal 《Molecular systems biology》2009,5(1)
Cellular functions are mediated through complex systems of macromolecules and metabolites linked through biochemical and physical interactions, represented in interactome models as ‘nodes’ and ‘edges’, respectively. Better understanding of genotype‐to‐phenotype relationships in human disease will require modeling of how disease‐causing mutations affect systems or interactome properties. Here we investigate how perturbations of interactome networks may differ between complete loss of gene products (‘node removal’) and interaction‐specific or edge‐specific (‘edgetic’) alterations. Global computational analyses of ~50 000 known causative mutations in human Mendelian disorders revealed clear separations of mutations probably corresponding to those of node removal versus edgetic perturbations. Experimental characterization of mutant alleles in various disorders identified diverse edgetic interaction profiles of mutant proteins, which correlated with distinct structural properties of disease proteins and disease mechanisms. Edgetic perturbations seem to confer distinct functional consequences from node removal because a large fraction of cases in which a single gene is linked to multiple disorders can be modeled by distinguishing edgetic network perturbations. Edgetic network perturbation models might improve both the understanding of dissemination of disease alleles in human populations and the development of molecular therapeutic strategies. 相似文献
96.
Luciano Neves de Medeiros Renata Angeli Carolina G. Sarzedas Ana Paula Valente Eleonora Kurtenbach 《生物化学与生物物理学报:生物膜》2010,1798(2):105-113
Plant defensins are cysteine-rich cationic peptides, components of the innate immune system. The antifungal sensitivity of certain exemplars was correlated to the level of complex glycosphingolipids in the membrane of fungi strains. Psd1 is a 46 amino acid residue defensin isolated from pea seeds which exhibit antifungal activity. Its structure is characterized by the so-called cysteine-stabilized α/β motif linked by three loops as determined by two-dimensional NMR. In the present work we explored the measurement of heteronuclear Nuclear Overhauser Effects, R1 and R2 15N relaxation ratios, and chemical shift to probe the backbone dynamics of Psd1 and its interaction with membrane mimetic systems with phosphatidylcholine (PC) or dodecylphosphocholine (DPC) with glucosylceramide (CMH) isolated from Fusarium solani. The calculated R2 values predicted a slow motion around the highly conserved among Gly12 residue and also in the region of the Turn3 His36-Trp38. The results showed that Psd1 interacts with vesicles of PC or PC:CMH in slightly different forms. The interaction was monitored by chemical shift perturbation and relaxation properties. Using this approach we could map the loops as the binding site of Psd1 with the membrane. The major binding epitope showed conformation exchange properties in the μs-ms timescale supporting the conformation selection as the binding mechanism. Moreover, the peptide corresponding to part of Loop1 (pepLoop1: Gly12 to Ser19) is also able to interact with DPC micelles acquiring a stable structure and in the presence of DPC:CMH the peptide changes to an extended conformation, exhibiting NOE mainly with the carbohydrate and ceramide parts of CMH. 相似文献
97.
Guoqiu Wu Hongbin Wu Linxian Li Jiaxuan Ding Tao Xi 《Biochemical and biophysical research communications》2010,395(1):31-35
Thanatin, a 21-residue peptide, is an inducible insect peptide. In our previous study, we have identified a novel thanatin analog of S-thanatin, which exhibited a broad antimicrobial activity against bacteria and fungi with low hemolytic activity. This study was aimed to delineate the antimicrobial mechanism of S-thanatin and identify its interaction with bacterial membranes. In this study, membrane phospholipid was found to be the target for S-thanatin. In the presence of vesicles, S-thanatin interestingly led to the aggregation of anionic vesicles and sonicated bacteria. Adding S-thanatin to Escherichia coli suspension would result in the collapse of membrane and kill bacteria. The sensitivity assay of protoplast elucidated the importance of outer membrane (OM) for S-thanatin’s antimicrobial activity. Compared with other antimicrobial peptide, S-thanatin produced chaotic membrane morphology and cell debris in electron microscopic appearance. These results supported our hypothesis that S-thanatin bound to negatively charged LPS and anionic lipid, impeded membrane respiration, exhausted the intracellular potential, and released periplasmic material, which led to cell death. 相似文献
98.
In this work, the conformational behavior of ribonuclease Sso7d is studied as a function of chirality of its constituting amino acids. Both optimized structures (using molecular mechanics with the CHARMM force field) and dynamic behavior (obtained by molecular dynamic simulations) are compared. 相似文献
99.
Ospdr9, which encodes a PDR-type ABC transporter, is induced by heavy metals, hypoxic stress and redox perturbations in rice roots 总被引:1,自引:0,他引:1
Moons A 《FEBS letters》2003,553(3):370-376
Little is known about the role of pleiotropic drug resistance (PDR)-type ATP-binding (ABC) proteins in plant responses to environmental stresses. We characterised ospdr9, which encodes a rice ABC protein with a reverse (ABC-TMS(6))(2) configuration. Polyethylene glycol and the heavy metals Cd (20 microM) and Zn (30 microM) rapidly and markedly induced ospdr9 in roots of rice seedlings. Hypoxic stress also induced ospdr9 in rice roots, salt stress induced ospdr9 at low levels but cold and heat shock had no effect. The plant growth regulator jasmonic acid, the auxin alpha-naphthalene acetic acid and the cytokinin 6-benzylaminopurine triggered ospdr9 expression. The antioxidants dithiothreitol and ascorbic acid rapidly and markedly induced ospdr9 in rice roots; the strong oxidant hydrogen peroxide also induced ospdr9 but at three times lower levels. The results suggested that redox changes may be involved in the abiotic stress response regulation of ospdr9 in rice roots. 相似文献
100.
Effect of methylation on the stability and solvation free energy of amylose and cellulose fragments: a molecular dynamics study 总被引:1,自引:0,他引:1
Yu H Amann M Hansson T Köhler J Wich G van Gunsteren WF 《Carbohydrate research》2004,339(10):1697-1709
Molecular dynamics (MD) simulations were used to study the stability and solvation of amylose and cellulose fragments. The recently developed gromos carbohydrate force field was further tested by simulating maltose, cellobiose, and maltoheptaose. The MD simulations reproduced fairly well the favorable conformations of disaccharides defined by the torsional angles related with the glycosidic bond and the radius gyration of maltoheptaose. The effects of methylation at different hydroxyl groups on the stability of amylose and cellulose fragments were investigated. The methylations of O-2 and O-3 reduce the stability of a single helix more than methylation at O-6, while the latter reduces the stability of a double helix more. Solvation free-energy differences between the unsubstituted amylose and cellulose fragments and the methylated species were studied using the single-step perturbation method. It was found that methylation at O-2 has the biggest effect, in agreement with experiment. 相似文献