The Experts below are selected from a list of 1464 Experts worldwide ranked by ideXlab platform
Rodney L. Levine - One of the best experts on this subject based on the ideXlab platform.
-
stereospecific oxidation of calmodulin by mEthionine sulfoxide reductase a
Free Radical Biology and Medicine, 2013Co-Authors: Rodney L. LevineAbstract:Abstract MEthionine sulfoxide reductase A has long been known to reduce S -mEthionine sulfoxide, both as a free amino acid and within proteins. Recently the enzyme was shown to be bidirectional, capable of oxidizing free mEthionine and mEthionine in proteins to S -mEthionine sulfoxide. A feasible mechanism for controlling the directionality has been proposed, raising the possibility that reversible oxidation and reduction of mEthionine residues within proteins is a redox-based mechanism for cellular regulation. We undertook studies aimed at identifying proteins that are subject to site-specific, stereospecific oxidation and reduction of mEthionine residues. We found that calmodulin, which has nine mEthionine residues, is such a substrate for mEthionine sulfoxide reductase A. When calmodulin is in its calcium-bound form, Met77 is oxidized to S -mEthionine sulfoxide by mEthionine sulfoxide reductase A. When mEthionine sulfoxide reductase A operates in the reducing direction, the oxidized calmodulin is fully reduced back to its native form. We conclude that reversible covalent modification of Met77 may regulate the interaction of calmodulin with one or more of its many targets.
-
mEthionine sulfoxide reductase a is a stereospecific mEthionine oxidase
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Rodney L. LevineAbstract:MEthionine sulfoxide reductase A (MsrA) catalyzes the reduction of mEthionine sulfoxide to mEthionine and is specific for the S epimer of mEthionine sulfoxide. The enzyme participates in defense against oxidative stresses by reducing mEthionine sulfoxide residues in proteins back to mEthionine. Because oxidation of mEthionine residues is reversible, this covalent modification could also function as a mechanism for cellular regulation, provided there exists a stereospecific mEthionine oxidase. We show that MsrA itself is a stereospecific mEthionine oxidase, producing S-mEthionine sulfoxide as its product. MsrA catalyzes its own autooxidation as well as oxidation of free mEthionine and mEthionine residues in peptides and proteins. When functioning as a reductase, MsrA fully reverses the oxidations which it catalyzes.
-
mEthionine residues may protect proteins from critical oxidative damage
Mechanisms of Ageing and Development, 1999Co-Authors: Rodney L. Levine, Jackob Moskovitz, Barbara S Berlett, Laurent Mosoni, Earl R StadtmanAbstract:Cysteine and mEthionine are the two sulfur-containing residues normally found in proteins. Cysteine residues function in the catalytic cycle of many enzymes, and they form disulfide bonds which contribute to protein structure. In contrast, the key functions of mEthionine residues are not known. We propose that mEthionine residues constitute an important antioxidant defense mechanism. A variety of oxidants react readily with mEthionine to form mEthionine sulfoxide, and surface exposed mEthionine residues create an extremely high concentration of reactant, providing for efficient scavenging of oxidants. The effect of hydrogen peroxide exposure upon glutamine synthetase from Escherichia coli was studied as an in vitro model system. Eight of the sixteen mEthionine residues could be oxidized with little effect on activity. The oxidizable mEthionine residues were found to be relatively surface exposed while the intact residues were generally buried within the core of the protein. Further, the susceptible residues were physically arranged in an array which guarded the entrance to the active site. MEthionine sulfoxide can be reduced back to mEthionine by the enzyme mEthionine sulfoxide reductase, providing a catalytic amplification of the antioxidant potential of each mEthionine residue. Given the importance of oxidative stress during aging, the potential function of mEthionine residues as antioxidants during aging should be investigated experimentally.
James Gomes - One of the best experts on this subject based on the ideXlab platform.
-
production of mEthionine by a multi analogue resistant mutant of corynebacterium lilium
Process Biochemistry, 2003Co-Authors: D Kumar, S Garg, V S Bisaria, T R Sreekrishnan, James GomesAbstract:Multi-analogue resistant mutants of Corynebacterium lilium were developed using UV and N -methyl-N ?-nitro-nitrosoguanidine (NTG) mutagenesis in order to overproduce mEthionine. Although the mEthionine yield at each stage of mutation by UV and NTG mutagenesis were comparable, it was observed that the NTG mutants had higher cell growth and glucose utilization rates. From the parent NTG mutant C. lilium E 4 resistant to Ethionine, the highest mEthionine producing strain C. lilium M-128 resistant to 3.5 mg ml � 1 of Ethionine, 3.0 mg ml � 1 of norleucine, 3.8 mg ml � 1 of mEthionine sulphoxide and 3.8 mg ml � 1 of mEthionine methyl sulphoniumchloride was derived. When C. lilium M-128 was grown under optimised conditions, it produced 2.3 g l � 1 of mEthionine in a 15 l batch reactor. The maximum cell mass concentration obtained was 17 g l � 1 dry cell weight resulting in a cell yield coefficient of 0.34 g g � 1 . The dissolved oxygen concentration was controlled at 40% saturation by cascade control of the airflow rate and agitation speed. # 2002 Elsevier Science Ltd. All rights reserved.
Jun Ogawa - One of the best experts on this subject based on the ideXlab platform.
-
l leucine 5 hydroxylase of nostoc punctiforme is a novel type of fe ii α ketoglutarate dependent dioxygenase that is useful as a biocatalyst
Applied Microbiology and Biotechnology, 2013Co-Authors: Makoto Hibi, Takashi Kawashima, Pavel Mikhailovich Sokolov, Sergey V Smirnov, Tomohiro Kodera, Masakazu Sugiyama, Sakayu Shimizu, Kenzo Yokozeki, Jun OgawaAbstract:l-Leucine 5-hydroxylase (LdoA) previously found in Nostoc punctiforme PCC 73102 is a novel type of Fe(II)/α-ketoglutarate-dependent dioxygenase. LdoA catalyzed regio- and stereoselective hydroxylation of l-leucine and l-norleucine into (2S,4S)-5-hydroxyleucine and (2S)-5-hydroxynorleucine, respectively. Moreover, LdoA catalyzed sulfoxidation of l-mEthionine and l-Ethionine in the same manner as previously described l-isoleucine 4-hydroxylase. Therefore LdoA should be a promising biocatalyst for effective production of industrially useful amino acids.
-
Characterization of Bacillus thuringiensis l-Isoleucine Dioxygenase for Production of Useful Amino Acids
Applied and environmental microbiology, 2011Co-Authors: Makoto Hibi, Takashi Kawashima, Pavel Mikhailovich Sokolov, Sergey V Smirnov, Tomohiro Kodera, Masakazu Sugiyama, Sakayu Shimizu, Kenzo Yokozeki, Jun OgawaAbstract:ABSTRACT We determined the enzymatic characteristics of an industrially important biocatalyst, α-ketoglutarate-dependent l-isoleucine dioxygenase (IDO), which was found to be the enzyme responsible for the generation of (2S,3R,4S)-4-hydroxyisoleucine in Bacillus thuringiensis 2e2. Depending on the amino acid used as the substrate, IDO catalyzed three different types of oxidation reactions: hydroxylation, dehydrogenation, and sulfoxidation. IDO stereoselectively hydroxylated several hydrophobic aliphatic l-amino acids, as well as l-isoleucine, and produced (S)-3-hydroxy-l-allo-isoleucine, 4-hydroxy-l-leucine, (S)-4-hydroxy-l-norvaline, 4-hydroxy-l-norleucine, and 5-hydroxy-l-norleucine. The IDO reaction product of l-isoleucine, (2S,3R,4S)-4-hydroxyisoleucine, was again reacted with IDO and dehydrogenated into (2S,3R)-2-amino-3-methyl-4-ketopentanoate, which is also a metabolite found in B. thuringiensis 2e2. Interestingly, IDO catalyzed the sulfoxidation of some sulfur-containing l-amino acids and generated l-mEthionine sulfoxide and l-Ethionine sulfoxide. Consequently, the effective production of various modified amino acids would be possible using IDO as the biocatalyst.
Ahmed Lebrihi - One of the best experts on this subject based on the ideXlab platform.
-
effect of amino acids containing sulfur on dithiolopyrrolone antibiotic productions by saccharothrix algeriensis nrrl b 24137
Journal of Applied Microbiology, 2006Co-Authors: Noureddine Bouras, Florence Mathieu, Nasserdine Sabaou, Ahmed LebrihiAbstract:Aims: To study the effect of sulfur-containing amino acids (L-cysteine, L-cystine, L-mEthionine and DL-Ethionine) on the production of dithiolopyrrolone antibiotics by Saccharothrix algeriensis NRRL B-24137. Methods and Results: The production levels of dithiolopyrrolones were investigated by using high performance liquid chromatography in a chemically semi-synthetic medium. The production of the studied antibiotics depends upon the nature, concentration and the time of addition of these sources in the culture medium. Both cysteine and cystine favoured the specific productions of dithiolopyrrolones; iso-butyryl-pyrrothine (ISP) by cysteine, however butanoyl-pyrrothine, senecioyl-pyrrothine and tigloyl-pyrrothine by cystine, when added initially to the culture medium. The maximum specific productions of dithiolopyrrolones were observed in the presence of 5 mmol l−1 cystine for thiolutin, 5 mmol l−1 cysteine for ISP, and 10 mmol l−1 cystine for others studied dithiolopyrrolones as shown in Fig. 3. The production of these antibiotics was decreased when the concentrations of cysteine and cystine were in excess. All dithiolopyrrolone specific productions were strongly inhibited by addition of mEthionine and Ethionine, without inhibition of mycelial growth. Figure 3. Effect of cysteine () and cystine () addition at different concentrations on specific production of thiolutin (a), senecioyl-pyrrothine (b), tigloyl-pyrrothine (c), iso-butyryl-pyrrothine (d) and butanoyl-pyrrothine (e). Specific dithiolopyrrolone productions are given as mg per g of biomass at the time of maximal productions during 96 h of fermentation. Download figure to PowerPoint Conclusions: Among all studied amino acids, cystine and cysteine can be used as supplements for improvement the production of dithiolopyrrolone antibiotics by S. algeriensis NRRL B-24137. Significance and Impact of the Study: Dithiolopyrrolone antibiotics have many important applications for employing them as medicaments, particularly in the treatment of human and animal cancers. In the present work, the influence of containing-sulfur amino acids on dithiolopyrrolone antibiotic productions was studied. The obtained results can be employed for the optimization of the culture medium for the dithiolopyrrolone productions in higher quantities.
D Kumar - One of the best experts on this subject based on the ideXlab platform.
-
production of mEthionine by a multi analogue resistant mutant of corynebacterium lilium
Process Biochemistry, 2003Co-Authors: D Kumar, S Garg, V S Bisaria, T R Sreekrishnan, James GomesAbstract:Multi-analogue resistant mutants of Corynebacterium lilium were developed using UV and N -methyl-N ?-nitro-nitrosoguanidine (NTG) mutagenesis in order to overproduce mEthionine. Although the mEthionine yield at each stage of mutation by UV and NTG mutagenesis were comparable, it was observed that the NTG mutants had higher cell growth and glucose utilization rates. From the parent NTG mutant C. lilium E 4 resistant to Ethionine, the highest mEthionine producing strain C. lilium M-128 resistant to 3.5 mg ml � 1 of Ethionine, 3.0 mg ml � 1 of norleucine, 3.8 mg ml � 1 of mEthionine sulphoxide and 3.8 mg ml � 1 of mEthionine methyl sulphoniumchloride was derived. When C. lilium M-128 was grown under optimised conditions, it produced 2.3 g l � 1 of mEthionine in a 15 l batch reactor. The maximum cell mass concentration obtained was 17 g l � 1 dry cell weight resulting in a cell yield coefficient of 0.34 g g � 1 . The dissolved oxygen concentration was controlled at 40% saturation by cascade control of the airflow rate and agitation speed. # 2002 Elsevier Science Ltd. All rights reserved.