LIVIVO - Search results -

Search results

Result 1 - 10 of total 25

Search options

Article: Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14

Nowak, Stefanie / Di Pizio, Antonella / Levit, Anat / Niv, Masha Y / Meyerhof, Wolfgang / Behrens, Maik

Biochimica et biophysica acta. 2018 Oct., v. 1862, no. 10

2018

Abstract: In humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute disproportionally high to ... ...

Abstract	In humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute disproportionally high to the perception of bitterness. Perhaps the most broadly tuned receptor is the TAS2R14, which may represent, because of its prominent expression in extraoral tissues, a receptor of particular importance for the physiological actions of bitter compounds beyond taste.To investigate how the architecture and composition of the TAS2R14 binding pocket enables specific interactions with a complex array of chemically diverse bitter agonists, we carried out homology modeling and ligand docking experiments, subjected the receptor to point-mutagenesis of binding site residues and performed functional calcium mobilization assays.In total, 40 point-mutated receptor constructs were generated to investigate the contribution of 19 positions presumably located in the receptor's binding pocket to activation by 7 different TAS2R14 agonists. All investigated positions exhibited moderate to pronounced agonist selectivity.Since numerous modifications of the TAS2R14 binding pocket resulted in improved responses to individual agonists, we conclude that this bitter taste receptor might represent a suitable template for the engineering of the agonist profile of a chemoreceptive receptor.The detailed structure-function analysis of the highly promiscuous and widely expressed TAS2R14 suggests that this receptor must be considered as potentially frequent target for known and novel drugs including undesired off-effects.
Keywords	agonists ; binding sites ; bitter-tasting compounds ; bitterness ; calcium ; drugs ; engineering ; humans ; ligands ; models ; mouth ; taste receptors ; tissues
Language	English
Dates of publication	2018-10
Size	p. 2162-2173.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	840755-1
ISSN	0304-4165
ISSN	0304-4165
DOI	10.1016/j.bbagen.2018.07.009
Database	NAL-Catalogue (AGRICOLA)

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uc I Zs.247: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: The Recognition of Unrelated Ligands by Identical Proteins.

Pottel, Joshua / Levit, Anat / Korczynska, Magdalena / Fischer, Marcus / Shoichet, Brian K

ACS chemical biology

2018 Volume 13, Issue 9, Page(s) 2522–2533

Abstract: Unrelated ligands, often found in drug discovery campaigns, can bind to the same receptor, even with the same protein residues. To investigate how this might occur, and whether it might be typically possible to find unrelated ligands for the same drug ... ...

Abstract	Unrelated ligands, often found in drug discovery campaigns, can bind to the same receptor, even with the same protein residues. To investigate how this might occur, and whether it might be typically possible to find unrelated ligands for the same drug target, we sought examples of topologically unrelated ligands that bound to the same protein in the same site. Seventy-six pairs of ligands, each bound to the same protein (152 complexes total), were considered, classified into three groups. In the first (31 pairs of complexes), unrelated ligands interacted largely with the same pocket residues through different functional groups. In the second group (39 pairs), the unrelated ligand in each pair engaged different residues, though still within the same pocket. The smallest group (6 pairs) contained ligands with different scaffolds but with shared functional groups interacting with the same residues. We found that there are multiple chemically unrelated but physically similar functional groups that can complement any given local protein pocket; when these functional group substitutions are combined within a single molecule, they lead to topologically unrelated ligands that can each well-complement a site. It may be that many active and orthosteric sites can recognize topologically unrelated ligands.
MeSH term(s)	Binding Sites ; Databases, Protein ; Drug Discovery/methods ; Humans ; Ligands ; Molecular Docking Simulation ; Protein Binding ; Proteins/chemistry ; Proteins/metabolism ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology
Chemical Substances	Ligands ; Proteins ; Small Molecule Libraries
Language	English
Publishing date	2018-08-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.8b00443
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone.

Wang, Sheng / Che, Tao / Levit, Anat / Shoichet, Brian K / Wacker, Daniel / Roth, Bryan L

Nature

2018 Volume 555, Issue 7695, Page(s) 269–273

Abstract: Dopamine is a neurotransmitter that has been implicated in processes as diverse as reward, addiction, control of coordinated movement, metabolism and hormonal secretion. Correspondingly, dysregulation of the dopaminergic system has been implicated in ... ...

Abstract	Dopamine is a neurotransmitter that has been implicated in processes as diverse as reward, addiction, control of coordinated movement, metabolism and hormonal secretion. Correspondingly, dysregulation of the dopaminergic system has been implicated in diseases such as schizophrenia, Parkinson's disease, depression, attention deficit hyperactivity disorder, and nausea and vomiting. The actions of dopamine are mediated by a family of five G-protein-coupled receptors. The D2 dopamine receptor (DRD2) is the primary target for both typical and atypical antipsychotic drugs, and for drugs used to treat Parkinson's disease. Unfortunately, many drugs that target DRD2 cause serious and potentially life-threatening side effects due to promiscuous activities against related receptors. Accordingly, a molecular understanding of the structure and function of DRD2 could provide a template for the design of safer and more effective medications. Here we report the crystal structure of DRD2 in complex with the widely prescribed atypical antipsychotic drug risperidone. The DRD2-risperidone structure reveals an unexpected mode of antipsychotic drug binding to dopamine receptors, and highlights structural determinants that are essential for the actions of risperidone and related drugs at DRD2.
MeSH term(s)	Antipsychotic Agents/chemistry ; Antipsychotic Agents/metabolism ; Binding Sites ; Crystallography, X-Ray ; Drug Design ; Humans ; Hydrophobic and Hydrophilic Interactions ; Kinetics ; Ligands ; Models, Molecular ; Mutant Proteins/chemistry ; Mutant Proteins/genetics ; Mutant Proteins/metabolism ; Mutation ; Receptors, Dopamine D2/chemistry ; Receptors, Dopamine D2/genetics ; Receptors, Dopamine D2/metabolism ; Receptors, Dopamine D3/chemistry ; Receptors, Dopamine D3/metabolism ; Receptors, Dopamine D4/chemistry ; Receptors, Dopamine D4/metabolism ; Risperidone/chemistry ; Risperidone/metabolism
Chemical Substances	Antipsychotic Agents ; Ligands ; Mutant Proteins ; Receptors, Dopamine D2 ; Receptors, Dopamine D3 ; Receptors, Dopamine D4 (137750-34-6) ; Risperidone (L6UH7ZF8HC)
Language	English
Publishing date	2018-01-24
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature25758
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 9: Show issues
Zs.MO 244: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14.

Nowak, Stefanie / Di Pizio, Antonella / Levit, Anat / Niv, Masha Y / Meyerhof, Wolfgang / Behrens, Maik

Biochimica et biophysica acta. General subjects

2018 Volume 1862, Issue 10, Page(s) 2162–2173

Abstract: Background: In humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute ... ...

Abstract	Background: In humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute disproportionally high to the perception of bitterness. Perhaps the most broadly tuned receptor is the TAS2R14, which may represent, because of its prominent expression in extraoral tissues, a receptor of particular importance for the physiological actions of bitter compounds beyond taste. Methods: To investigate how the architecture and composition of the TAS2R14 binding pocket enables specific interactions with a complex array of chemically diverse bitter agonists, we carried out homology modeling and ligand docking experiments, subjected the receptor to point-mutagenesis of binding site residues and performed functional calcium mobilization assays. Results: In total, 40 point-mutated receptor constructs were generated to investigate the contribution of 19 positions presumably located in the receptor's binding pocket to activation by 7 different TAS2R14 agonists. All investigated positions exhibited moderate to pronounced agonist selectivity. Conclusions: Since numerous modifications of the TAS2R14 binding pocket resulted in improved responses to individual agonists, we conclude that this bitter taste receptor might represent a suitable template for the engineering of the agonist profile of a chemoreceptive receptor. General significance: The detailed structure-function analysis of the highly promiscuous and widely expressed TAS2R14 suggests that this receptor must be considered as potentially frequent target for known and novel drugs including undesired off-effects.
MeSH term(s)	Amino Acid Sequence ; Aristolochic Acids/chemistry ; Aristolochic Acids/metabolism ; Binding Sites ; Humans ; Ligands ; Models, Molecular ; Molecular Docking Simulation ; Monoterpenes/chemistry ; Monoterpenes/metabolism ; Mutagenesis, Site-Directed ; Mutation ; Picrotoxin/analogs & derivatives ; Picrotoxin/chemistry ; Picrotoxin/metabolism ; Protein Binding ; Protein Conformation ; Protein Engineering ; Receptors, G-Protein-Coupled/agonists ; Receptors, G-Protein-Coupled/chemistry ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Taste/physiology
Chemical Substances	Aristolochic Acids ; Ligands ; Monoterpenes ; Receptors, G-Protein-Coupled ; taste receptors, type 2 ; Picrotoxin (124-87-8) ; beta-thujone (8ZI5R3T54Q) ; aristolochic acid I (94218WFP5T) ; picrotoxinin (9K011NUF0R)
Language	English
Publishing date	2018-07-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0304-4165 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0304-4165 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2018.07.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uc I Zs.247: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Structural identification of a hotspot on CFTR for potentiation.

Liu, Fangyu / Zhang, Zhe / Levit, Anat / Levring, Jesper / Touhara, Kouki K / Shoichet, Brian K / Chen, Jue

Science (New York, N.Y.)

2019 Volume 364, Issue 6446, Page(s) 1184–1188

Abstract: Cystic fibrosis is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Two main categories of drugs are being developed: correctors that improve folding of CFTR and potentiators that recover the function ...

Abstract	Cystic fibrosis is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Two main categories of drugs are being developed: correctors that improve folding of CFTR and potentiators that recover the function of CFTR. Here, we report two cryo-electron microscopy structures of human CFTR in complex with potentiators: one with the U.S. Food and Drug Administration (FDA)-approved drug ivacaftor at 3.3-angstrom resolution and the other with an investigational drug, GLPG1837, at 3.2-angstrom resolution. These two drugs, although chemically dissimilar, bind to the same site within the transmembrane region. Mutagenesis suggests that in both cases, hydrogen bonds provided by the protein are important for drug recognition. The molecular details of how ivacaftor and GLPG1837 interact with CFTR may facilitate structure-based optimization of therapeutic compounds.
MeSH term(s)	Aminophenols/chemistry ; Aminophenols/pharmacology ; Binding Sites ; Chloride Channel Agonists/chemistry ; Chloride Channel Agonists/pharmacology ; Chloride Channel Agonists/therapeutic use ; Cryoelectron Microscopy ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis Transmembrane Conductance Regulator/chemistry ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Drugs, Investigational/chemistry ; Drugs, Investigational/pharmacology ; Drugs, Investigational/therapeutic use ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Mutagenesis ; Protein Domains ; Protein Folding/drug effects ; Pyrans/chemistry ; Pyrans/pharmacology ; Pyrans/therapeutic use ; Pyrazoles/chemistry ; Pyrazoles/pharmacology ; Pyrazoles/therapeutic use ; Quinolones/chemistry ; Quinolones/pharmacology
Chemical Substances	Aminophenols ; CFTR protein, human ; Chloride Channel Agonists ; Drugs, Investigational ; GLPG1837 ; Pyrans ; Pyrazoles ; Quinolones ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; ivacaftor (1Y740ILL1Z)
Language	English
Publishing date	2019-06-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aaw7611
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Comparing Class A GPCRs to bitter taste receptors: Structural motifs, ligand interactions and agonist-to-antagonist ratios.

Di Pizio, Antonella / Levit, Anat / Slutzki, Michal / Behrens, Maik / Karaman, Rafik / Niv, Masha Y

Methods in cell biology

2016 Volume 132, Page(s) 401–427

Abstract: G protein-coupled receptors (GPCRs) are seven transmembrane (TM) proteins that play a key role in human physiology. The GPCR superfamily comprises about 800 members, classified into several classes, with rhodopsin-like Class A being the largest and most ... ...

Abstract	G protein-coupled receptors (GPCRs) are seven transmembrane (TM) proteins that play a key role in human physiology. The GPCR superfamily comprises about 800 members, classified into several classes, with rhodopsin-like Class A being the largest and most studied thus far. A huge component of the human repertoire consists of the chemosensory GPCRs, including ∼400 odorant receptors, 25 bitter taste receptors (TAS2Rs), which are thought to guard the organism from consuming poisons, and sweet and umami TAS1R heteromers, which indicate the nutritive value of food. The location of the binding site of TAS2Rs is similar to that of Class A GPCRs. However, most of the known bitter ligands are agonists, with only a few antagonists documented thus far. The agonist-to-antagonist ratios of Class A GPCRs vary, but in general are much lower than for TAS2Rs. For a set of well-studied GPCRs, a gradual change in agonists-to-antagonists ratios is observed when comparing low (10 μM)- and high (10 nM)-affinity ligand sets from ChEMBL and the DrugBank set of drugs. This shift reflects pharmaceutical bias toward the therapeutically desirable pharmacology for each of these GPCRs, while the 10 μM sets possibly represent the native tendency of the receptors toward either agonists or antagonists. Analyzing ligand-GPCR interactions in 56 X-ray structures representative of currently available structural data, we find that the N-terminus, TM1 and TM2 are more involved in binding of antagonists than of agonists. On the other hand, ECL2 tends to be more involved in binding of agonists. This is of interest, since TAS2Rs harbor variations on the typical Class A sequence motifs, including the absence of the ECL2-TM3 disulfide bridge. This suggests an alternative mode of regulation of conformational states for TAS2Rs, with potentially less stabilized inactive state. The comparison of TAS2Rs and Class A GPCRs structural features and the pharmacology of the their ligands highlights the intricacies of GPCR architecture and provides a framework for rational design of new ligands.
MeSH term(s)	Binding Sites ; Humans ; Ligands ; Models, Molecular ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/agonists ; Receptors, G-Protein-Coupled/antagonists & inhibitors ; Receptors, G-Protein-Coupled/chemistry ; Taste/drug effects
Chemical Substances	Ligands ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2016
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	0091-679X
ISSN	0091-679X
DOI	10.1016/bs.mcb.2015.10.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Corrigendum: Independent Evolution of Strychnine Recognition by Bitter Taste Receptor Subtypes.

Xue, Ava Yuan / Di Pizio, Antonella / Levit, Anat / Yarnitzky, Tali / Penn, Osnat / Pupko, Tal / Niv, Masha Y

Frontiers in molecular biosciences

2018 Volume 5, Page(s) 84

Abstract: This corrects the article DOI: 10.3389/fmolb.2018.00009.]. ...

Abstract	[This corrects the article DOI: 10.3389/fmolb.2018.00009.].
Language	English
Publishing date	2018-09-11
Publishing country	Switzerland
Document type	Journal Article ; Published Erratum
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2018.00084
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Independent Evolution of Strychnine Recognition by Bitter Taste Receptor Subtypes.

Xue, Ava Yuan / Di Pizio, Antonella / Levit, Anat / Yarnitzky, Tali / Penn, Osnat / Pupko, Tal / Niv, Masha Y

Frontiers in molecular biosciences

2018 Volume 5, Page(s) 9

Abstract: The 25 human bitter taste receptors (hT2Rs) recognize thousands of structurally and chemically diverse bitter substances. The binding modes of human bitter taste receptors hT2R10 and hT2R46, which are responsible for strychnine recognition, were ... ...

Abstract	The 25 human bitter taste receptors (hT2Rs) recognize thousands of structurally and chemically diverse bitter substances. The binding modes of human bitter taste receptors hT2R10 and hT2R46, which are responsible for strychnine recognition, were previously established using site-directed mutagenesis, functional assays, and molecular modeling. Here we construct a phylogenetic tree and reconstruct ancestral sequences of the T2R10 and T2R46 clades. We next analyze the binding sites in view of experimental data to predict their ability to recognize strychnine. This analysis suggests that the common ancestor of hT2R10 and hT2R46 is unlikely to bind strychnine in the same mode as either of its two descendants. Estimation of relative divergence times shows that hT2R10 evolved earlier than hT2R46. Strychnine recognition was likely acquired first by the earliest common ancestor of the T2R10 clade before the separation of primates from other mammals, and was highly conserved within the clade. It was probably independently acquired by the common ancestor of T2R43-47 before the homo-ape speciation, lost in most T2Rs within this clade, but enhanced in the hT2R46 after humans diverged from the rest of primates. Our findings suggest hypothetical strychnine T2R receptors in several species, and serve as an experimental guide for further study. Improved understanding of how bitter taste receptors acquire the ability to be activated by particular ligands is valuable for the development of sensors for bitterness and for potential toxicity.
Language	English
Publishing date	2018-03-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2018.00009
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Homology modeling of G-protein-coupled receptors with X-ray structures on the rise.

Yarnitzky, Talia / Levit, Anat / Niv, Masha Y

Current opinion in drug discovery & development

2010 Volume 13, Issue 3, Page(s) 317–325

Abstract: GPCRs are key components of signal transduction pathways and are important drug targets. Recently determined GPCR structures provide opportunities for advancements in GPCR modeling. This review focuses on the choice of experimental templates, the ... ...

Abstract	GPCRs are key components of signal transduction pathways and are important drug targets. Recently determined GPCR structures provide opportunities for advancements in GPCR modeling. This review focuses on the choice of experimental templates, the treatment of extracellular loops and the description of ligand-binding sites in GPCR modeling. Four important conclusions are reached in this review: (i) multi-template models may produce better structures than single-template models, although inferior models may also be generated by multi-template approaches, warranting the development and application of improved model assessment methods; (ii) cautious incorporation of knowledge-based constraints can improve the quality of models and docking; (iii) molecular dynamics simulations account for structural features not observed in X-ray structures and may refine docking poses; and (iv) while progress in de novo methods for long loop prediction is ongoing, loopless models provide a practical alternative for docking and virtual screening applications.
MeSH term(s)	Binding Sites ; Computer Simulation ; Crystallography, X-Ray/methods ; Drug Discovery/methods ; Ligands ; Models, Structural ; Molecular Dynamics Simulation ; Protein Conformation ; Receptors, G-Protein-Coupled/chemistry ; Sequence Homology, Amino Acid
Chemical Substances	Ligands ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2010-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1461136-3
ISSN	2040-3437 ; 1367-6733
ISSN (online)	2040-3437
ISSN	1367-6733
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5276: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Expression and structure/function relationships of human defensin 5.

Chapnik, Nava / Levit, Anat / Niv, Masha Y / Froy, Oren

Applied biochemistry and biotechnology

2012 Volume 166, Issue 7, Page(s) 1703–1710

Abstract: The innate immunity utilizes a battery of broad-spectrum antibacterial cationic polypeptides (3-5 kDa), among them defensins. In humans, defensins are the first line of defense against pathogens and their expression has been implicated in several ... ...

Abstract	The innate immunity utilizes a battery of broad-spectrum antibacterial cationic polypeptides (3-5 kDa), among them defensins. In humans, defensins are the first line of defense against pathogens and their expression has been implicated in several diseases. The antibacterial activity of defensins is generally ascribed to their overall positive charge, which enables them to disrupt bacterial membrane integrity and function, but their active surface has not been fully elucidated. To perform structural and functional assays, an efficient, high-yield, easy-to-use expression and purification system must be established. Up to now, most efforts to obtain larger quantities of active recombinant defensins have been only moderately successful. Herein, we report the establishment of an efficient, high-yield expression and purification system for human defensin 5 (HD-5). Using site-directed mutagenesis, we pinpoint several arginine residues and Y27 as important for HD-5 antibacterial activity. Our expression and purification system can be harnessed for structure/activity relationship studies of defensins in particular and small polypeptides in general.
MeSH term(s)	Amino Acid Sequence ; Anti-Bacterial Agents/biosynthesis ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Arginine/genetics ; Chromatography, High Pressure Liquid ; Cloning, Molecular ; Escherichia coli ; Gene Expression ; Humans ; Microbial Viability/drug effects ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation ; Plasmids ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/pharmacology ; Static Electricity ; Structure-Activity Relationship ; alpha-Defensins/chemistry ; alpha-Defensins/genetics ; alpha-Defensins/pharmacology
Chemical Substances	Anti-Bacterial Agents ; DEFA5 protein, human ; Recombinant Proteins ; alpha-Defensins ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2012-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	392344-7
ISSN	1559-0291 ; 0273-2289
ISSN (online)	1559-0291
ISSN	0273-2289
DOI	10.1007/s12010-012-9571-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 3053: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito