Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MACROMOLECULAR SYSTEMS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed2002

Free-energy component analysis of 40 protein-DNA complexes: a consensus view on the thermodynamics of binding at the molecular level.

Noncovalent association of proteins to specific target sites on DNA--a process central to gene expression and regulation--has thus far proven to be idiosyncratic and elusive to generalizations on the nature of the driving forces. The spate of structural information on protein--DNA complexes sets the stage for theoretical investigations on the molecular thermodynamics of binding aimed at identifying forces responsible for specific macromolecular recognition. Computation of absolute binding free energies for systems of this complexity transiting from structural information is a stupendous task. Adopting some recent progresses in treating atomic level interactions in proteins and nucleic acids including solvent and salt effects, we have put together an energy component methodology cast in a phenomenological mode and amenable to systematic improvements and developed a computational first atlas of the free energy contributors to binding in approximately 40 protein-DNA complexes representing a variety of structural motifs and functions. Illustrating vividly the compensatory nature of the free energy components contributing to the energetics of recognition for attaining optimal binding, our results highlight unambiguously the roles played by packing, electrostatics including hydrogen bonds, ion and water release (cavitation) in protein-DNA binding. Cavitation and van der Waals contributions without exception favor complexation. The electrostatics is marginally unfavorable in a consensus view. Basic residues on the protein contribute favorably to binding despite the desolvation expense. The electrostatics arising from the acidic and neutral residues proves unfavorable to binding. An enveloping mode of binding to short stretches of DNA makes for a strong unfavorable net electrostatics but a highly favorable van der Waals and cavitation contribution. Thus, noncovalent protein-DNA association is a system-specific fine balancing act of these diverse competing forces. With the advances in computational methods as applied to macromolecular recognition, the challenge now seems to be to correlate the differential (initial vs. final) energetics to substituent effects in drug design and to move from affinity to specificity.

Algorithms↗
PubMed1987

The next frontier in the molecular biology of the opioid system. The opioid receptors.

The analgesic and euphoric properties of some plant alkaloids such as morphine have been known and exploited for centuries. In contrast, only during the last twenty years have we begun to unravel the molecular basis by which opiates exert their effects, mechanisms important to our general understanding of the nervous system. The analgesic response to opiates is the result of a cascade of biochemical events that are triggered by the interaction of the opiate with specific macromolecular components found on the membranes of nervous system tissues, the opioid receptors. The endogenous ligands of these receptors are small peptides, the opioid peptides. Although much has been learned about the structures and the mode of synthesis of the opioid peptides, little is understood about the structure of their receptors. The application of molecular genetic techniques was of great importance to the studies of the opioid peptides. It is now expected that this same technology will unravel the physical mysteries of the opioid receptors.

Animals↗
PubMed1994

Differential expression of beta 1, beta 3, and beta 4 integrin subunits in nonneoplastic neural cells of the peripheral and autonomic nervous system and in tumors derived from these cells.

BACKGROUND: Extracellular matrix proteins and their receptors take part in physiologic neural development and organization and also in abnormal neoplastic growth and spread. There is increasing evidence for the implication of integrins in these processes. EXPERIMENTAL DESIGN: Human tissues containing nonneoplastic neural cells of the peripheral and autonomic nervous system and a comprehensive series of neural tumors were examined for the in situ expression of beta 1, beta 3, and beta 4 integrins. Serial frozen sections of each tissue sample were immunostained using an indirect streptavidin/biotin-peroxidase method and monoclonal antibodies against beta 1, alpha 1 to alpha 6, beta 3, alpha v, and beta 4 subunits. RESULTS: Both small- and large-diameter nerve fibers of normal peripheral nerve trunks were consistently beta 1+, alpha 6+, and beta 4+ in the absence of alpha 3, alpha 4, alpha 5, and beta 3. Small-diameter nerve fibers further expressed alpha 1, alpha 2, and alpha v. Meissner's corpuscles and inner cores of Pacinian corpuscles shared the integrin repertoire of small-diameter nerve fibers with additional expression of alpha 3; outer cores of Pacinian corpuscles were beta 1+, alpha 3+, alpha 6+, and beta 4+. Regenerating nerve fibers paralleled the integrin profile of normal peripheral nerves. By contrast, malignant schwannomas showed considerable changes in integrin expression. These alterations consisted mainly in a neoexpression of alpha 3, alpha 4, and alpha 5 and in an abnormal loss of alpha 6 and beta 4. Expression of alpha 1, alpha 2, and alpha v was variable; absence of beta 3 was generally conserved. In ganglion cells, integrin expression was restricted to beta 1 and alpha 3 subunits, and chromaffine cells of the adrenal medulla even lacked any detectable beta 1, beta 3, and beta 4 integrin subunits. (Ganglio)-neuroblastomas, however, were beta 1+, alpha 1+, and alpha 3+, whereas primitive peripheral neuroectodermal tumors were beta 1+ and alpha 5+. CONCLUSIONS: Nonneoplastic human neural cells exhibit a complex and, at the same time, differential pattern of beta 1, beta 3, and beta 4 integrin subunit expression. Malignant transformation leads to considerable changes in this integrin profile. The observation of neoplasia-associated abnormalities underlines the important role of integrins in the orderly development and maintenance of human neural tissue. Some aspects of the emerging integrin subunit patterns are useful for the differential diagnosis of neural soft-tissue tumors.

Adrenal Glands↗
PubMed1987

Pathophysiology of intestinal uptake and absorption of antigens in food allergy.

An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of proteins and protein fragments. To combat the potential danger of invasion across the mucosal barrier, the infant must develop within the lumen and on the luminal mucosal surface an elaborate system of defense mechanisms that act to control and maintain the epithelium as an impermeable barrier to the uptake of macromolecular antigens. These defenses include a unique local immunologic system adapted to function in the complicated milieu of the intestine as well as other nonimmunologic processes such as a gastric barrier, intestinal surface secretions, peristaltic movement, etc, all of which help to provide maximum protection for the intestinal surface. Unfortunately, during the immediate postpartum period, especially for premature and "small-for-date" infants, this elaborate local defense system is incompletely developed. As a result of the delay in the maturation of the mucosal barrier, newborn infants are particularly vulnerable to pathologic penetration by harmful intraluminal substances. The consequences of altered defense are susceptibility to infection and the potential for hypersensitivity reactions and the formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis, and hepatitis. Fortunately, nature has provided a means for passively protecting the "vulnerable" newborn against the dangers of a deficient intestinal defense system: human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leukocytes, but many other substances that can interfere with bacterial colonization and prevent antigen penetration.

Antigens↗
PubMed1975

[The self-organization of biological structures (author's transl)].

Viruses played an important role in analysing macromolecular structures. Structure and function in living systems are arranged hierarchically. An important purpose of biology is to describe the correlation between the structural hierarchy and the observed assembly and to analyse the embryological program of the organism.

Adenylate Kinase↗
PubMed1992

Detection of receptor-ligand interactions using surface plasmon resonance: model studies employing the HIV-1 gp120/CD4 interaction.

Surface plasmon resonance (SPR), a label-free, real time optical detection principle, has been investigated for its potential to detect and quantitate macromolecular ligand-ligate interactions. As model systems, the interactions of the HIV-1 envelope glycoprotein, gp120, and the monoclonal antibody L-71, with a soluble form of the T-cell receptor CD4 (sCD4), were investigated. In an effort to demonstrate potential analytical applications of this technology, operational characteristics of the SPR instrumentation (BIAcore, Pharmacia) including stability of the sensing surface and reproducibility in the measurement of such macromolecular interactions were investigated. In addition, the ability to detect and quantitate sCD4 directly from unfractionated cell culture supernatants, such as Streptomyces lividans, was investigated. The results demonstrate that SPR has potential in quantitating macromolecular interactions in both purified and crude samples and that the reproducibility in, and sensitivity of, such determinations is comparable to other techniques.

Antibodies, Monoclonal↗
PubMed1965

PHENETHYL ALCOHOL. I. EFFECT ON MACROMOLECULAR SYNTHESIS OF ESCHERICHIA COLI.

Rosenkranz, Herbert S. (Columbia University, New York, N.Y.), Howard S. Carr, and Harry M. Rose. Phenethyl alcohol. I. Effect on macromolecular synthesis of Escherichia coli. J. Bacteriol. 89:1354-1369. 1965.-An investigation of the mode of action of phenethyl alcohol produced the following results. Phenethyl alcohol had no effect on the physicochemical properties of isolated deoxyribonucleic acid (DNA). The DNA isolated from phenethyl alcohol-treated bacteria had physicochemical properties identical with those of DNA isolated from normal cells. The metabolic functions most sensitive to the inhibitory action of phenethyl alcohol appeared to be the process of enzyme induction and, possibly, the synthesis of messenger ribonucleic acid. Phenethyl alcohol did not affect the polyuridylic acid-mediated synthesis of polyphenylalanine in a cell-free amino acid-incorporating system.

Alcohols↗
PubMed2002

Sorting signals from protein NMR spectra: SPI, a Bayesian protocol for uncovering spin systems.

Grouping of spectral peaks into J-connected spin systems is essential in the analysis of macromolecular NMR data as it provides the basis for disentangling chemical shift degeneracies. It is a mandatory step before resonance and NOESY cross-peak identities can be established. We have developed SPI, a computational protocol that scrutinizes peak lists from homo- and hetero-nuclear multidimensional NMR spectra and progressively assembles sets of resonances into consensus J- and/or NOE-connected spin systems. SPI estimates the likelihood of nuclear spin resonances appearing at defined frequencies given sets of cross-peaks measured from multi-dimensional experiments. It quantifies spin system matching probabilities via Bayesian inference. The protocol takes advantage of redundancies in the number of connectivities revealed by suites of diverse NMR experiments, systematically tracking the adequacy of each grouping hypothesis. SPI was tested on 2D homonuclear and 2D/3D(15)N-edited data recorded from two protein modules, the col 2 domain of matrix metalloproteinase-2 (MMP-2) and the kringle 2 domain of plasminogen, of 60 and 83 amino acid residues, respectively. For these protein domains SPI identifies approximately 95% unambiguous resonance frequencies, a relatively good performance vis-à-vis the reported 'manual' (interactive) analyses. Abbreviations and Acronyms: SPI, SPin Identification; BMRB, BioMagResBank (Madison, WI).

Amino Acid Sequence↗
PubMed1989

Transport through deformable matrices.

In order to induce and maintain a pressure gradient in a fluid mixture in steady state, the fluid has to pass through a solid-like matrix capable of generating and carrying an extra stress gradient. Frictional interactions between fluid components and the matrix then produce separations. Matrix deformation occurs and the implication of this is discussed. A general solution for multicomponent systems is given and then specialised to the case of three components--a deformable gel matrix component, a solvent and a macromolecular solute. A method is given for solving the system of equations and is applied in the steady state. Applications involving transendothelial flow and self-regulated selectivity are stressed in particular. The calculations are based on the Flory-Huggins equation, on the Flory gel deformation model and on ad hoc, very crude approximations to the concentration dependence of the three, pairwise defined friction coefficients between the three components involved.

Biological Transport↗
PubMed2003

Mycobacterium tuberculosis Hsp16.3 nonamers are assembled and re-assembled via trimer and hexamer intermediates.

Hsp16.3, a small heat shock protein from Mycobacterium tuberculosis proposed to form specific trimer-of-trimers structures, acts as a molecular chaperone in vitro. The assembly and re-assembly mechanisms of this oligomeric protein were studied and compared using in vitro transcription/translation and denaturization/renaturization systems. Analysis using a combination of non-denaturing pore gradient polyacrylamide gel electrophoresis, chemical cross-linking, and size-exclusion chromatography demonstrate that the predominant form of Hsp16.3 produced in the in vitro transcription/translation system is the trimer, which can be further assembled into a nonameric structure via a hexamer intermediate in the presence of purified exogenous Hsp16.3 proteins. Meanwhile, an "inert" Hsp16.3 dimer, which does not seem to participate in nonamer assembly but may be involved in forming other forms of Hsp16.3, was also detected in the in vitro expression system. On the other hand, our current data clearly show that the re-assembly of Hsp16.3 nonamers also occurs via a very similar mechanism, with the formation of trimers and hexamers. The presence of high levels of macromolecular crowding protein agent in the in vitro expression system promoted the formation of the nonamers to a very limited degree, indicating that the assembly of proteins like Hsp16.3 may depend mainly on its own concentration instead of those of the macromolecules in the environment.

Bacterial Proteins↗
PubMed1993

Principles of functional and structural organization in the bacterial cell: 'compartments' and their enzymes.

Most bacteria lack obvious compartmentation, i.e., structural partition of the cell into functional entities (organelles) formed by a closed biological membrane. Nevertheless, these organisms exhibit sophisticated regulation and interactions of their catabolic and anabolic pathways; they are able to exploit a great variety of carbon and energy sources, and they conserve and transform energy in an efficient manner. In a less stringent sense, 'compartments' are also present in bacteria if one accepts that bacterial 'compartments' are not necessarily surrounded by a membrane, but are rather defined as mere functional entities characterized by their structural components, their enzymes and other functional proteins such as binding proteins. This view would mean that the bacterial cell can be described as a highly organized structured system comprised of these functional entities. Regulated transport processes within 'compartments' and across boundaries involving low and high molecular mass compounds, solutes, and ions take place within the 'framework' constituted by this structured system. Special emphasis is given to the fact that many of the transport processes take place involving the functional entity 'energized membrane'. This 'framework', the structural basis for the functional potential of a bacterial cell, can be studied by electron microscopy. Advanced sample preparation techniques and imaging modes are available which keep the danger of artefact formation low; they can be applied at cellular and macromolecular levels. Recent developments in immunoelectron microscopy and affinity labelling techniques provide tools which allow to unequivocally locate enzymes and other antigens in the cell and to identify polypeptide chains in enzyme complexes. Application of these approaches in studies on cellular and macromolecular organization of bacteria and their enzyme systems confirmed some old views but also extended our knowledge. This is exemplified by a description of selected enzyme complexes located in the bacterial cytoplasm, in the cytoplasmic membrane or attached to it, in the periplasmic space, and attached to the cell wall or set free into the surrounding medium.

Aldehyde Oxidoreductases↗
PubMed2000

Molecular assembly and disassembly: novel photolabile molecular hosts

A new approach to the assembly and photochemical disassembly of molecular hosts is developed. It is based on photoinduced fragmentation in hydroxyalkyl dithianes and utilizes a novel spiro-bis-dithiane as a photolabile molecular tether to link two formylated macromolecular blocks, e.g., formyl calixarenes or formyl dibenzocrown ethers. A key feature of this molecular system is that after an assembly-disassembly cycle the starting macromolecular blocks are recovered intact and can be used again.

Journal Article↗
PubMed2005

Targeted delivery of antibodies through the blood-brain barrier by MRI-guided focused ultrasound.

The blood-brain barrier (BBB) is a persistent obstacle for the local delivery of macromolecular therapeutic agents to the central nervous system (CNS). Many drugs that show potential for treating CNS diseases cannot cross the BBB and there is a need for a non-invasive targeted drug delivery method that allows local therapy of the CNS using larger molecules. We developed a non-invasive technique that allows the image-guided delivery of antibody across the BBB into the murine CNS. Here, we demonstrate that subsequent to MRI-targeted focused ultrasound induced disruption of BBB, intravenously administered dopamine D(4) receptor-targeting antibody crossed the BBB and recognized its antigens. Using MRI, we were able to monitor the extent of BBB disruption. This novel technology should be useful in delivering macromolecular therapeutic or diagnostic agents to the CNS for the treatment of various CNS disorders.

Animals↗
PubMed1979

Studies of macromolecular heterogeneous associations involving cross-linking: a re-examination of the ovalbumin-lysozyme system.

A system is considered in which a multivalent acceptor interacts with a bivalent ligand in solution to form an array of complexes via multiple binding and cross-linking reactions. With the use of reacted site probability functions expressions are derived in terms of a site binding constant which are of potential use in the interpretation of sedimentation equilibrium and binding results obtained with such systems. Their potential use is explored in relation to results obtained on the interacting ovalbumin-lysozyme system at pH 6.80, ionic strength 0.02. A comparison is made of this interpretation with that based on an interaction pattern involving only multiple binding of ligand in the absence of cross-linking effects. While both interpretations quantitatively describe certain results, it is shown, by invoking further experimental observations on apparent weight-average molecular weight and precipitation behavior, that the more favored interpretation is that involving the operation of a spectrum of forces leading to a large array of ovalbumin-lysozyme complexes, including those of the cross-linked type. It is stressed that the particular ovalbumin-lysozyme system is but one example of interaction between oppositely charged macromolecules and therefore that the derived equations may find wider application to such systems and those known to involve more specific cross-linking interactions.

Chemical Phenomena↗
PubMed2003

Leucine/isoleucine zipper coordination of ion channel macromolecular signaling complexes in the heart. Roles in inherited arrhythmias.

The sympathetic nervous system controls the force and rate of contraction of the heart. The rapid response to stress and exercise mediated by increased sympathetic nervous system (SNS) activity requires the coordinated regulation of several ion channels in response to activation of beta-adrenergic receptors. The microenvironment of target channels is mediated by the assembly of macromolecular signaling complexes in which targeting proteins recruit phosphatases and kinases and in turn bind directly to the channel protein via highly conserved leucine/isoleucine zippers (LIZs). Disruption of local signaling by disease-associated LIZ mutations unbalances the physiologic response to SNS stimulation and increases the risk of arrhythmia in mutation carriers.

Arrhythmias, Cardiac↗
PubMed2005

Auto-rickshaw: an automated crystal structure determination platform as an efficient tool for the validation of an X-ray diffraction experiment.

The EMBL-Hamburg Automated Crystal Structure Determination Platform is a system that combines a number of existing macromolecular crystallographic computer programs and several decision-makers into a software pipeline for automated and efficient crystal structure determination. The pipeline can be invoked as soon as X-ray data from derivatized protein crystals have been collected and processed. It is controlled by a web-based graphical user interface for data and parameter input, and for monitoring the progress of structure determination. A large number of possible structure-solution paths are encoded in the system and the optimal path is selected by the decision-makers as the structure solution evolves. The processes have been optimized for speed so that the pipeline can be used effectively for validating the X-ray experiment at a synchrotron beamline.

Crystallography, X-Ray↗
PubMed2002

NFAT signaling: choreographing the social lives of cells.

Calcium signaling activates the phosphatase calcineurin and induces movement of NFATc proteins into the nucleus, where they cooperate with other proteins to form complexes on DNA. Nuclear import is opposed by kinases such as GSK3, thereby rendering transcription continuously responsive to receptor occupancy. Disruptions of the genes involved in NFAT signaling are implicating this pathway as a regulator of developmental cell-cell interactions.

Active Transport, Cell Nucleus↗