scholarly journals CFTR: New insights into structure and function and implications for modulation by small molecules

2020 ◽  
Vol 19 ◽  
pp. S19-S24 ◽  
Author(s):  
Bertrand Kleizen ◽  
John F. Hunt ◽  
Isabelle Callebaut ◽  
Tzyh-Chang Hwang ◽  
Isabelle Sermet-Gaudelus ◽  
...  
Keyword(s):  
Small Molecules ◽  
Structure And Function ◽  
And Function

scholarly journals Susceptibility of protein therapeutics to spontaneous chemical modifications by oxidation, cyclization, and elimination reactions

Amino Acids ◽  
2019 ◽  
Vol 51 (10-12) ◽  
pp. 1409-1431 ◽  
Author(s):  
Luigi Grassi ◽  
Chiara Cabrele
Keyword(s):  
Small Molecules ◽  
Three Dimensional ◽  
Drug Market ◽  
Structure And Function ◽  
Dimensional Structure ◽  
Chemical Modifications ◽  
Small Molecule Drugs ◽  
And Function ◽  
The Impact

Abstract Peptides and proteins are preponderantly emerging in the drug market, as shown by the increasing number of biopharmaceutics already approved or under development. Biomolecules like recombinant monoclonal antibodies have high therapeutic efficacy and offer a valuable alternative to small-molecule drugs. However, due to their complex three-dimensional structure and the presence of many functional groups, the occurrence of spontaneous conformational and chemical changes is much higher for peptides and proteins than for small molecules. The characterization of biotherapeutics with modern and sophisticated analytical methods has revealed the presence of contaminants that mainly arise from oxidation- and elimination-prone amino-acid side chains. This review focuses on protein chemical modifications that may take place during storage due to (1) oxidation (methionine, cysteine, histidine, tyrosine, tryptophan, and phenylalanine), (2) intra- and inter-residue cyclization (aspartic and glutamic acid, asparagine, glutamine, N-terminal dipeptidyl motifs), and (3) β-elimination (serine, threonine, cysteine, cystine) reactions. It also includes some examples of the impact of such modifications on protein structure and function.

scholarly journals Towards a native environment: structure and function of membrane proteins in lipid bilayers by NMR

2021 ◽  
Author(s):  
Kai Xue ◽  
Kumar Tekwani Movellan ◽  
Xizhou Cecily Zhang ◽  
Eszter E. Najbauer ◽  
Marcel C. Forster ◽  
...  
Keyword(s):  
Solid State ◽  
Membrane Proteins ◽  
Small Molecules ◽  
Lipid Bilayers ◽  
Biological Samples ◽  
Solid State Nmr ◽  
Structure And Function ◽  
Versatile Technique ◽  
And Function

Solid-state NMR (ssNMR) is a versatile technique that can be used for the characterization of various materials, ranging from small molecules to biological samples, including membrane proteins, as reviewed here.

IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells

2000 ◽  
Vol 279 (5) ◽  
pp. G851-G857 ◽  
Author(s):  
A. Nusrat ◽  
J. R. Turner ◽  
J. L. Madara
Keyword(s):  
Small Molecules ◽  
Paracellular Permeability ◽  
Structure And Function ◽  
Epithelial Permeability ◽  
Multiprotein Complex ◽  
Permeable Barrier ◽  
Extracellular Stimuli ◽  
And Function ◽  
Tissue Compartments ◽  
Rate Limiting

The epithelial lining of the gastrointestinal tract forms a regulated, selectively permeable barrier between luminal contents and the underlying tissue compartments. Permeability across the epithelium is, in part, determined by the rate-limiting barrier of the paracellular pathway—the most apical intercellular junction referred to as the tight junction (TJ). The TJ is composed of a multiprotein complex that affiliates with the underlying apical actomyosin ring. TJ structure and function, and therefore epithelial permeability, are influenced by diverse physiological and pathological stimuli; here we review examples of such stimuli that are detected at the cell surface. For example, luminal glucose induces an increase in paracellular permeability to small molecules. Similarly, but by other means, cytokines and leukocytes in the vicinity of the epithelium also regulate TJ structure and paracellular permeability by influencing the TJ protein complex and/or its association with the underlying actin cytoskeleton.

scholarly journals Computational Modeling of Claudin Structure and Function

2020 ◽  
Vol 21 (3) ◽  
pp. 742 ◽  
Author(s):  
Shadi Fuladi ◽  
Ridaka-Wal Jannat ◽  
Le Shen ◽  
Christopher R. Weber ◽  
Fatemeh Khalili-Araghi
Keyword(s):  
Small Molecules ◽  
Tight Junctions ◽  
Barrier Function ◽  
Functional Model ◽  
Structure And Function ◽  
Structural Basis ◽  
Crystallographic Structure ◽  
Epithelial Barrier Function ◽  
Transport Of Ions ◽  
And Function

Tight junctions form a barrier to control passive transport of ions and small molecules across epithelia and endothelia. In addition to forming a barrier, some of claudins control transport properties of tight junctions by forming charge- and size-selective ion channels. It has been suggested claudin monomers can form or incorporate into tight junction strands to form channels. Resolving the crystallographic structure of several claudins in recent years has provided an opportunity to examine structural basis of claudins in tight junctions. Computational and theoretical modeling relying on atomic description of the pore have contributed significantly to our understanding of claudin pores and paracellular transport. In this paper, we review recent computational and mathematical modeling of claudin barrier function. We focus on dynamic modeling of global epithelial barrier function as a function of claudin pores and molecular dynamics studies of claudins leading to a functional model of claudin channels.

scholarly journals Small Molecules Targeting the Hedgehog Pathway: From Phenotype to Mechanistic Understanding

2020 ◽  
Vol 74 (9) ◽  
pp. 652-658 ◽  
Author(s):  
Sascha Hoogendoorn
Keyword(s):  
Small Molecules ◽  
Cell Biology ◽  
Developmental Disorders ◽  
Interdisciplinary Approach ◽  
Structure And Function ◽  
Target Deconvolution ◽  
And Function ◽  
The University ◽  
New Compounds ◽  
Biology Lab

Since the beginning of 2019, the Hoogendoorn lab is active at the University of Geneva. We are a Chemical Biology lab and our research focuses on the Hedgehog (Hh) signalling pathway and the primary cilium, a small cellular organelle which corrects structure and function, is required to conduct the Hh signal. Ciliary Hh signalling plays an important role in embryonic development, and its dysregulation consequently results in developmental disorders as well as a variety of cancers. We use an interdisciplinary approach, ranging from organic chemistry to cell biology and genetics, to develop chemical tools to study and perturb ciliary signalling. In this account, I will highlight existing small molecules that target the Hh pathway, our efforts to discover new compounds, and the methodologies that we employ for target deconvolution and mechanism of action studies.

MolBridge: a program for identifying nonbonded interactions in small molecules and biomolecular structures

2014 ◽  
Vol 47 (5) ◽  
pp. 1772-1776 ◽  
Author(s):  
Prasun Kumar ◽  
Senthilkumar Kailasam ◽  
Shaunak Chakraborty ◽  
Manju Bansal
Keyword(s):  
Small Molecules ◽  
Halogen Bond ◽  
Three Dimensional ◽  
Web Server ◽  
Structure And Function ◽  
Structural Studies ◽  
Nonbonded Interactions ◽  
Three Dimensional Coordinate ◽  
And Function ◽  
The Web

Identification and analysis of nonbonded interactions within a molecule and with the surrounding molecules are an essential part of structural studies, given the importance of these interactions in defining the structure and function of any supramolecular entity.MolBridgeis an easy to use algorithm based purely on geometric criteria that can identify all possible nonbonded interactions, such as hydrogen bond, halogen bond, cation–π, π–π and van der Waals, in small molecules as well as biomolecules. The user can either upload three-dimensional coordinate files or enter the molecular ID corresponding to the relevant database. The program is available in a standalone form and as an interactive web server withJmolandJMEincorporated into it. The program is freely downloadable and the web server version is also available at http://nucleix.mbu.iisc.ernet.in/molbridge/index.php.

Structure and function of neural networks in the retina

1988 ◽  
Vol 46 ◽  
pp. 26-27
Author(s):  
Peter Sterling
Keyword(s):  
Ganglion Cells ◽  
Three Dimensional ◽  
Structure And Function ◽  
Synaptic Connections ◽  
Visual Axis ◽  
One Dimensional ◽  
Cat Retina ◽  
Ultrathin Sections ◽  
And Function ◽  
Insight Into

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.

Osseointegration interface of calcified bone and endosseous implants

1992 ◽  
Vol 50 (2) ◽  
pp. 1096-1097
Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley
Keyword(s):  
Structure And Function ◽  
Titanium Implants ◽  
En Bloc ◽  
Endosseous Implants ◽  
Ultrastructural Studies ◽  
The Past ◽  
Cacodylate Buffer ◽  
One Year ◽  
And Function

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.

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