961 research outputs found
Sulfatases
No full textDierks T. Sulfatases. In: Creighton TE, ed. Encyclopedia of Molecular Medicine. New York: J. Wiley; 2001: 3042-3046
Arylsulfatases
No full textDierks T, Schmidt B. Arylsulfatases. In: Creighton TE, ed. Encyclopedia of Molecular Medicine. New York: J. Wiley; 2001: 266-268
Cysteine-modifying enzyme
No full textDierks T. Cysteine-modifying enzyme. In: Creighton TE, ed. Encyclopedia of Molecular Medicine. New York: J. Wiley; 2001: 974-976
Arylsulfatase G, a novel lysosomal sulfatase
No full textFrese M-A, Schulz S, Dierks T. Arylsulfatase G, a novel lysosomal sulfatase. JOURNAL OF BIOLOGICAL CHEMISTRY. 2008;283(17):11388-11395.The sulfatases constitute a conserved family of enzymes that specifically hydrolyze sulfate esters in a wide variety of substrates such as glycosaminoglycans, steroid sulfates, or sulfolipids. By modifying the sulfation state of their substrates, sulfatases play a key role in the control of physiological processes, including cellular degradation, cell signaling, and hormone regulation. The loss of sulfatase activity has been linked with various severe pathophysiological conditions such as lysosomal storage disorders, developmental abnormalities, or cancer. A novel member of this family, arylsulfatase G (ASG), was initially described as an enzyme lacking in vitro arylsulfatase activity and localizing to the endoplasmic reticulum. Contrary to these results, we demonstrate here that ASG does indeed have arylsulfatase activity toward different pseudosubstrates like p-nitrocatechol sulfate and 4-methylumbelliferyl sulfate. The activity of ASG depends on the Cys-84 residue that is predicted to be post-translationally converted to the critical active site C-alpha-formylglycine. Phosphate acts as a strong, competitive ASG inhibitor. ASG is active as an unprocessed 63-kDa monomer and shows an acidic pH optimum as typically seen for lysosomal sulfatases. In transfected cells, ASG accumulates within lysosomes as indicated by indirect immunofluorescence microscopy. Furthermore, ASG is a glycoprotein that binds specifically to mannose 6-phosphate receptors, corroborating its lysosomal localization. ARSG mRNA expression was found to be tissue-specific with highest expression in liver, kidney, and pancreas, suggesting a metabolic role of ASG that might be associated with a so far non-classified lysosomal storage disorder
ASYMMETRIC ORIENTATION OF THE RECONSTITUTED ASPARTATE GLUTAMATE CARRIER FROM MITOCHONDRIA
No full textDierks T, KRAMER R. ASYMMETRIC ORIENTATION OF THE RECONSTITUTED ASPARTATE GLUTAMATE CARRIER FROM MITOCHONDRIA. BIOCHIMICA ET BIOPHYSICA ACTA. 1988;937(1):112-126
Task demand modulations of visuospatial processing measured with functional magnetic resonance imaging
No full textBrain imaging based on functional magnetic resonance imaging (fMRI) provides a useful tool to examine neural networks and cerebral structures subserving visuospatial function. It allows not only the qualitative determination of which areas are active during task processing, but also estimates the quantitative contribution of involved brain regions to different aspects of spatial processing. In this study, we investigated in 10 healthy subjects how the amount of task (computational) demand in an angle discrimination task was related to neural activity as measured with event-related fMRI. Task demand, indicated by behavioral performance, was modulated by presenting clocks with different angular disparity and length of hands. Significant activations were found in the cortical network subserving the visual and visuospatial processing, including the right and left superior parietal lobules (SPL), striate visual areas, and sensorimotor areas. Both blood oxygenation level-dependent (BOLD) signal strength and spatial extent of activation in right as well as left SPL increased with task demand. By contrast, no significant correlation or a very weak correlation was found between the task demand and the BOLD signal as well as between task demand and spatial extent of activations in the striate visual areas and in the sensorimotor areas. These results support the hypothesis that increased computational demand requires more brain resources. The brain regions that are most specialized for the execution of the visuospatial task can be assessed by relating the imposed task demand to the functional activation measured. (C) 2003 Elsevier Inc. All rights reserved
REACTION-MECHANISM OF THE RECONSTITUTED ASPARTATE GLUTAMATE CARRIER FROM BOVINE HEART-MITOCHONDRIA
No full textDierks T, RIEMER E, KRAMER R. REACTION-MECHANISM OF THE RECONSTITUTED ASPARTATE GLUTAMATE CARRIER FROM BOVINE HEART-MITOCHONDRIA. BIOCHIMICA ET BIOPHYSICA ACTA. 1988;943(2):231-244
Sulf loss influences N-, 2-O-, and 6-O-sulfation of multiple heparan sulfate proteoglycans and modulates fibroblast growth factor signaling
No full textLamanna WC, Frese M-A, Balleininger M, Dierks T. Sulf loss influences N-, 2-O-, and 6-O-sulfation of multiple heparan sulfate proteoglycans and modulates fibroblast growth factor signaling. JOURNAL OF BIOLOGICAL CHEMISTRY. 2008;283(41):27724-27735.Sulf1 and Sulf2 are two heparan sulfate 6-O-endosulfatases that regulate the activity of multiple growth factors, such as fibroblast growth factor and Wnt, and are essential for mammalian development and survival. In this study, the mammalian Sulfs were functionally characterized using overexpressing cell lines, in vitro enzyme assays, and in vivo Sulf knock-out cell models. Analysis of subcellular Sulf localization revealed significant differences in enzyme secretion and detergent solubility between the human isoforms and their previously characterized quail orthologs. Further, the activity of the Sulfs toward their native heparan sulfate substrates was determined in vitro, demonstrating restricted specificity for S-domain-associated 6S disaccharides and an inability to modify transition zone-associated UA-GlcNAc( 6S). Analysis of heparan sulfate composition from different cell surface, shed, glycosylphosphatidylinositol- anchored and extracellular matrix proteoglycan fractions of Sulf knock-out cell lines established differential effects of Sulf1 and/or Sulf2 loss on nonsubstrate N-, 2-O-, and 6-O-sulfate groups. These findings indicate a dynamic influence of Sulf deficiency on the HS biosynthetic machinery. Real time PCR analysis substantiated differential expression of the Hs2st and Hs6st heparan sulfate sulfotransferase enzymes in the Sulf knock-out cell lines. Functionally, the changes in heparan sulfate sulfation resulting from Sulf loss were shown to elicit significant effects on fibroblast growth factor signaling. Taken together, this study implicates that the Sulfs are involved in a potential cellular feed-back mechanism, in which they edit the sulfation of multiple heparan sulfate proteoglycans, thereby regulating cellular signaling and modulating the expression of heparan sulfate biosynthetic enzymes
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