Advertisement

Topics

L-Arginine hydrochloride increases the solubility of folded and unfolded recombinant plasminogen activator rPA.

06:00 EDT 29th July 2010 | BioPortfolio

Summary of "L-Arginine hydrochloride increases the solubility of folded and unfolded recombinant plasminogen activator rPA."

L-Arginine hydrochloride (L-ArgHCl) was found to be an effective enhancer for in vitro protein refolding more than two decades ago. A detailed understanding of the mechanism of action, by which L-ArgHCl as co-solvent is capable to effectively suppress protein aggregation, while protein stability is preserved, has remained elusive. Concepts for the effects of co-solvents, which have been established over the last decades, were found to be insufficient to completely explain the effects of L-ArgHCl on protein refolding.In this paper we present data, which clearly establish that L-ArgHCl acts on the equilibrium solubility of the native model protein rPA, while for S-carboxymethylated rPA (IAA-rPA) that served as a model protein for denatured protein states, equilibrium solubilities could not be obtained. Solid to solute free transfer energies for native rPA were lowered by up to 14 kJ mol(-1) under the tested conditions. This finding is in marked contrast to a previously proposed model in which L-ArgHCl acts as a neutral crowder which exclusively has an influence on the stability of the transition state of aggregation. The effects on the apparent solubility of IAA-rPA as well as on the aggregation kinetics of all studied protein species that were observed in the present work could tentatively explained within the framework of a nucleation-aggregation scheme, in which L-ArgHCl exerts a strong effect on the pre-equilibria leading to formation of the aggregation seed.

Affiliation

Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany.

Journal Details

This article was published in the following journal.

Name: Protein science : a publication of the Protein Society
ISSN: 1469-896X
Pages:

Links

DeepDyve research library

PubMed Articles [1577 Associated PubMed Articles listed on BioPortfolio]

Broken TALEs: Transcription Activator-like Effectors Populate Partly Folded States.

Transcription activator-like effector proteins (TALEs) contain large numbers of repeats that bind double-stranded DNA, wrapping around DNA to form a continuous superhelix. Since unbound TALEs retain s...

Probing Small Molecule Binding to Unfolded Polyprotein Based on its Elasticity and Refolding.

Unfolded protein, a disordered structure found before folding of newly synthesized protein or after protein denaturation, is a substrate for binding by many cellular factors such as heat-stable protei...

Bacterial Inner-membrane Display for Screening a Library of Antibody Fragments.

Antibodies engineered for intracellular function must not only have affinity for their target antigen, but must also be soluble and correctly folded in the cytoplasm. Commonly used methods for the dis...

SODA: prediction of protein solubility from disorder and aggregation propensity.

Solubility is an important, albeit not well understood, feature determining protein behavior. It is of paramount importance in protein engineering, where similar folded proteins may behave in very dif...

Effect of poly-L-arginine in inhibiting scrapie prion protein of cultured cells.

Biological effect of poly-L-arginine (PLR), the linear homopolymer comprised of L-arginine, was investigated to determine the activity of suppressing prions. PLR decreased the level of scrapie prion p...

Clinical Trials [2007 Associated Clinical Trials listed on BioPortfolio]

Supplementation of L-arginine in Patients With Non-resectable Brain Metastases

This study evaluates the nutritional supplement arginine as supportive measure for patients with unresectable metastatic brain tumors that receive radiation therapy with palliative intent

A Study of ProMetic Plasminogen IV Infusion in Subjects With Hypoplasminogenemia

This is a Phase 2/3 pivotal study of ProMetic Plasminogen (Human) Intravenous Lyophilized solution. The primary objective of the study is to achieve a consistent increase of individual tr...

N-Acetylcysteine and Arginine Administration in Diabetic Patients

It has been demonstrated that the nitric oxide production is reduced in type 2 diabetic patients and that cardiovascular complications represent 80% of the causes of death in these patient...

Arginine Treatment of Acute Chest Syndrome (Pneumonia) in Sickle Cell Disease Patients

This is a study to determine if oral arginine will increase nitric oxide in sickle cell disease (SCD) patients with acute chest syndrome (ACS). It will also assess the effects of arginine ...

Arginine Malaria Trial: Study of Adjunctive Arginine in Falciparum Malaria

Acute falciparum malaria is associated with low plasma arginine and impaired nitric oxide (NO) production. Both are associated with poor outcome. This study will examine the safety and eff...

Medical and Biotech [MESH] Definitions

Protein translocase in BACTERIA or CHLOROPLASTS that exports or secretes folded proteins. In GRAM-NEGATIVE BACTERIA, twin-arginine translocase (TAT) is involved in the export of folded proteins to the PERIPLASM. In chloroplasts, TAT is involved in transporting folded proteins across the membranes of THYLAKOIDS.

A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES.

A cellular response to environmental insults that cause disruptions in PROTEIN FOLDING and/or accumulation of defectively folded protein in the ENDOPLASMIC RETICULUM. It consists of a group of regulatory cascades that are triggered as a response to altered levels of calcium and/or the redox state of the endoplasmic reticulum. Persistent activation of the unfolded protein response leads to the induction of APOPTOSIS.

Conformational transitions of a protein from unfolded states to a more folded state.

Important modulators of the activity of plasminogen activators. Four inhibitors, all belonging to the serpin family of proteins, have been implicated in plasminogen activation inhibition. They are PAI-1; PAI-2; protease-nexin; and PROTEIN C INHIBITOR; (PAI-3). All inhibit both the tissue-type and urokinase-type plasminogen activators.

Quick Search
Advertisement
 


DeepDyve research library

Relevant Topic

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...


Searches Linking to this Article