The Experts below are selected from a list of 111 Experts worldwide ranked by ideXlab platform
Aaron J Oakley - One of the best experts on this subject based on the ideXlab platform.
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structural insights into omega class glutathione transferases a snapshot of enzyme reduction and identification of a non catalytic Ligandin site
PLOS ONE, 2013Co-Authors: Joseph Brock, Philip G Board, Aaron J OakleyAbstract:Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathionedependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reaction result in the formation of a mixed-disulfide of the enzyme with glutathione through the catalytic cysteine (C32). Recycling of the enzyme utilizes a second glutathione molecule and results in oxidized glutathione (GSSG) release. The crystal structure of an active-site mutant (C32A) of the hGSTO1-1 isozyme in complex with GSSG provides a snapshot of the enzyme in the process of regeneration. GSSG occupies both the G (GSH-binding) and H (hydrophobic-binding) sites and causes re-arrangement of some H-site residues. In the same structure we demonstrate the existence of a novel ‘‘Ligandin’’ binding site deep within in the dimer interface of this enzyme, containing S-(4nitrophenacyl)glutathione, an isozyme-specific substrate for hGSTO1-1. The Ligandin site, conserved in Omega class GSTs from a range of species, is hydrophobic in nature and may represent the binding location for tocopherol esters that are uncompetitive hGSTO1-1 inhibitors.
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the Ligandin non substrate binding site of human pi class glutathione transferase is located in the electrophile binding site h site
Journal of Molecular Biology, 1999Co-Authors: Aaron J Oakley, Lo M Bello, Marzia Nuccetelli, A P Mazzetti, Michael W ParkerAbstract:Glutathione S -transferases (GSTs) play a pivotal role in the detoxification of foreign chemicals and toxic metabolites. They were originally termed Ligandins because of their ability to bind large molecules (molecular masses >400 Da), possibly for storage and transport roles. The location of the Ligandin site in mammalian GSTs is still uncertain despite numerous studies in recent years. Here we show by X-ray crystallography that the Ligandin binding site in human pi class GST P1-1 occupies part of one of the substrate binding sites. This work has been extended to the determination of a number of enzyme complex crystal structures which show that very large ligands are readily accommodated into this substrate binding site and in all, but one case, causes no significant movement of protein side-chains. Some of these molecules make use of a hitherto undescribed binding site located in a surface pocket of the enzyme. This site is conserved in most, but not all, classes of GSTs suggesting it may play an important functional role.
V Müller - One of the best experts on this subject based on the ideXlab platform.
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sequence of subunit a of the na translocating f1f0 atpase of acetobacterium woodii proposal for residues involved in na binding
FEBS Letters, 1999Co-Authors: S Rahlfs, V MüllerAbstract:Na+ transport through the F0 domain of Na+-F1F0-ATPases involves the combined action of subunits c and a but the residues involved in Na+ Liganding in subunit a are unknown. As a first step towards the identification of these residues, we have cloned and sequenced the gene encoding subunit a of the Na+-F1F0-ATPase of Acetobacterium woodii. This is the second sequence available now for this subunit from Na+-F1F0-ATPases. A comparison of subunit a from Na+-F1F0-ATPases with those from H+-translocating enzymes unraveled structural similarity in a C-terminal segment including the ultimate and penultimate transmembrane helix. Seven residues are conserved in this region and, therefore, likely to be involved in Na+ Liganding.
R E Kirsch - One of the best experts on this subject based on the ideXlab platform.
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radioimmunoassay of human Ligandin
Hepatology, 2007Co-Authors: Morris Sherman, Nathan M Bass, John A H Campbell, R E KirschAbstract:A sensitive and specific radioimmunoassay for human Ligandin has been developed and used to study Ligandin release into the serum in acute and chronic hepatitis. Serum Ligandin concentrations were elevated in 67 of 68 cases of acute viral hepatitis. Ligandin levels frequently returned to normal within the first 2 weeks of illness. The rapid disappearance of Ligandin preceded the return to normal of serum SGOT. In chronic active hepatitis, serum Ligandin levels correlated significantly (p less than 0.01) with histologic severity of disease. This correlation was not seen with SGOT. Serum Ligandin may be useful in monitoring progress and the need for therapy in chronic active hepatitis.
Michael W Parker - One of the best experts on this subject based on the ideXlab platform.
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the Ligandin non substrate binding site of human pi class glutathione transferase is located in the electrophile binding site h site
Journal of Molecular Biology, 1999Co-Authors: Aaron J Oakley, Lo M Bello, Marzia Nuccetelli, A P Mazzetti, Michael W ParkerAbstract:Glutathione S -transferases (GSTs) play a pivotal role in the detoxification of foreign chemicals and toxic metabolites. They were originally termed Ligandins because of their ability to bind large molecules (molecular masses >400 Da), possibly for storage and transport roles. The location of the Ligandin site in mammalian GSTs is still uncertain despite numerous studies in recent years. Here we show by X-ray crystallography that the Ligandin binding site in human pi class GST P1-1 occupies part of one of the substrate binding sites. This work has been extended to the determination of a number of enzyme complex crystal structures which show that very large ligands are readily accommodated into this substrate binding site and in all, but one case, causes no significant movement of protein side-chains. Some of these molecules make use of a hitherto undescribed binding site located in a surface pocket of the enzyme. This site is conserved in most, but not all, classes of GSTs suggesting it may play an important functional role.
Wei Zhang - One of the best experts on this subject based on the ideXlab platform.
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purification molecular cloning and characterization of glutathione s transferases gsts from pigmented vitis vinifera l cell suspension cultures as putative anthocyanin transport proteins
Journal of Experimental Botany, 2008Co-Authors: Simon J Conn, Chris Curtin, Annie Bezier, Christopher M M Franco, Wei ZhangAbstract:The Ligandin activity of specific glutathione S-transferases (GSTs) is necessary for the transport of anthocyanins from the cytosol to the plant vacuole. Five GSTs were purified from Vitis vinifera L. cv. Gamay Freaux cell suspension cultures by glutathione affinity chromatography. These proteins underwent Edman sequencing and mass spectrometry fingerprinting, with the resultant fragments aligned with predicted GSTs within public databases. The corresponding coding sequences were cloned, with heterologous expression in Escherichia coli used to confirm GST activity. Transcriptional profiling of these candidate GST genes and key anthocyanin biosynthetic pathway genes (PAL, CHS, DFR, and UFGT) in cell suspensions and grape berries against anthocyanin accumulation demonstrated strong positive correlation with two sequences, VvGST1 and VvGST4, respectively. The ability of VvGST1 and VvGST4 to transport anthocyanins was confirmed in the heterologous maize bronze-2 complementation model, providing further evidence for their function as anthocyanin transport proteins in grape cells. Furthermore, the differential induction of VvGST1 and VvGST4 in suspension cells and grape berries suggests functional differences between these two proteins. Further investigation of these candidate Ligandins may identify a mechanism for manipulating anthocyanin accumulation in planta and in vitro suspension cells.