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.

The Relationship Between Structure and Function of Tight Junctions

2001 ◽  
Author(s):  
Lorenza González-Mariscal ◽  
Antonia Avila ◽  
Abigail Betanzos
Keyword(s):  
Tight Junctions ◽  
Structure And Function ◽  
And Function ◽  
The Relationship

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 NTPDase1 and -2 are expressed by distinct cellular compartments in the mouse colon and differentially impact colonic physiology and function after DSS colitis

2019 ◽  
Vol 317 (3) ◽  
pp. G314-G332 ◽  
Author(s):  
Vladimir Grubišić ◽  
Alberto L. Perez-Medina ◽  
David E. Fried ◽  
Jean Sévigny ◽  
Simon C. Robson ◽  
...  
Keyword(s):  
Barrier Function ◽  
Nucleoside Triphosphate ◽  
Gut Motility ◽  
Epithelial Barrier Function ◽  
Functional Roles ◽  
Dss Colitis ◽  
Health And Disease ◽  
And Function ◽  
Cellular Compartments ◽  
Catalytic Functions

ATP is both an important mediator of physiological gut functions such as motility and epithelial function, and a key danger signal that mediates cell death and tissue damage. The actions of extracellular ATP are regulated through the catalytic functions extracellular nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), -2, -3, and -8, which ultimately generate nucleosides. Ectonucleotidases have distinct cellular associations, but the specific locations and functional roles of individual NTPDases in the intestine are still poorly understood. Here, we tested the hypothesis that differential and cell-selective regulation of purine hydrolysis by NTPDase1 and -2 plays important roles in gut physiology and disease. We studied Entpd1 and Entpd2 null mice in health and following colitis driven by 2% dextran sulfate sodium (DSS) administration using functional readouts of gut motility, epithelial barrier function, and neuromuscular communication. NTPDase1 is expressed by immune cells, and the ablation of Entpd1 altered glial numbers in the myenteric plexus. NTPDase2 is expressed by enteric glia, and the ablation of Entpd2 altered myenteric neuron numbers. Mice lacking either NTPDase1 or -2 exhibited decreased inhibitory neuromuscular transmission and altered components of inhibitory junction potentials. Ablation of Entpd2 increased gut permeability following inflammation. In conclusion, the location- and context-dependent extracellular nucleotide phosphohydrolysis by NTPDase1 and -2 substantially impacts gut function in health and disease. NEW & NOTEWORTHY Purines are important mediators of gastrointestinal physiology and pathophysiology. Nucleoside triphosphate diphosphohydrolases (NTPDases) regulate extracellular purines, but the roles of specific NTPDases in gut functions are poorly understood. Here, we used Entpd1- and Entpd2-deficient mice to show that the differential and cell-selective regulation of purine hydrolysis by NTPDase1 and -2 plays important roles in barrier function, gut motility, and neuromuscular communication in health and disease.

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 Understanding the impacts of self-shuffling approach on structure and function of shuffled endoglucanase enzyme via MD simulations

2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Aslı Yenenler ◽  
Umut Gerlevik ◽  
Ugur Sezerman
Keyword(s):  
Experimental Studies ◽  
Salt Bridge ◽  
Md Simulations ◽  
Structure And Function ◽  
Computational Approach ◽  
Intramolecular Interactions ◽  
Structural Basis ◽  
Functional Differences ◽  
Structural Differences ◽  
And Function

AbstractObjectiveWe identify the impacts of structural differences on functionality of EG3_S2 endoglucanase enzyme with MD studies. The results of previous experimental studies have been explained in details with computational approach. The objective of this study is to explain the functional differences between shuffled enzyme (EG3_S2) and its native counterpart (EG3_nat) from Trichoderma reseei, via Molecular Dynamics approach.Materials and methodsFor this purpose, we performed MD simulations along 30 ns at three different reaction temperatures collected as NpT ensemble, and then monitored the backbone motion, flexibilities of residues, and intramolecular interactions of EG3_S2 and EG3_nat enzymes.ResultsAccording to MD results, we conclude that EG3_S2 and EG3_nat enzymes have unique RMSD patterns, e.g. RMSD pattern of EG3_S2 is more dynamic than that of EG3_nat at all temperatures. In addition to this dynamicity, EG3_S2 establishes more salt bridge interactions than EG3_nat.ConclusionBy taking these results into an account with the preservation of catalytic Glu residues in a proper manner, we explain the structural basis of differences between shuffled and native enzyme via molecular dynamic studies.

scholarly journals Structural Basis of Redox Signaling in Photosynthesis: Structure and Function of Ferredoxin:thioredoxin Reductase and Target Enzymes

2004 ◽  
Vol 79 (3) ◽  
pp. 233-248 ◽  
Author(s):  
Shaodong Dai ◽  
Kenth Johansson ◽  
Myroslawa Miginiac-Maslow ◽  
Peter Schürmann ◽  
Hans Eklund
Keyword(s):  
Redox Signaling ◽  
Structure And Function ◽  
Structural Basis ◽  
And Function ◽  
Ferredoxin:Thioredoxin Reductase
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