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13 results on '"Luebben, Anna V."'

1. Cln5 represents a new type of cysteine-based S-depalmitoylase linked to neurodegeneration

Author

Luebben, Anna, V, Bender, Daniel, Becker, Stefan, Crowther, Lisa M., Erven, Ilka, Hofmann, Kay, Soeding, Johannes, Klemp, Henry, Bellotti, Cristina, Stauble, Andreas, Qiu, Tian, Kathayat, Rahul S., Dickinson, Bryan C., Gaertner, Jutta, Sheldrick, George M., Kraetzner, Ralph, Steinfeld, Robert, Luebben, Anna, V, Bender, Daniel, Becker, Stefan, Crowther, Lisa M., Erven, Ilka, Hofmann, Kay, Soeding, Johannes, Klemp, Henry, Bellotti, Cristina, Stauble, Andreas, Qiu, Tian, Kathayat, Rahul S., Dickinson, Bryan C., Gaertner, Jutta, Sheldrick, George M., Kraetzner, Ralph, and Steinfeld, Robert

Abstract

Genetic CLN5 variants are associated with childhood neurodegeneration and Alzheimer's disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase (S-depalmitoylation) activity using fluorescent substrates. Mutational analysis revealed that the predicted catalytic residues histidine-166 and cysteine-280 are critical for Cln5 thioesterase activity, uncovering a new cysteine-based catalytic mechanism for S-depalmitoylation enzymes. Last, we found that Cln5-deficient neuronal progenitor cells showed reduced thioesterase activity, confirming live cell function of Cln5 in setting S-depalmitoylation levels. Our results provide new insight into the function of Cln5, emphasize the importance of S-depalmitoylation in neuronal homeostasis, and disclose a new, unexpected enzymatic function for the N1pC/P60 superfamily of proteins.

Published
2022

2. Cln5 represents a new type of cysteine-basedS-depalmitoylase linked to neurodegeneration

Author

Luebben, Anna V., primary, Bender, Daniel, additional, Becker, Stefan, additional, Crowther, Lisa M., additional, Erven, Ilka, additional, Hofmann, Kay, additional, Söding, Johannes, additional, Klemp, Henry, additional, Bellotti, Cristina, additional, Stäuble, Andreas, additional, Qiu, Tian, additional, Kathayat, Rahul S., additional, Dickinson, Bryan C., additional, Gärtner, Jutta, additional, Sheldrick, George M., additional, Krätzner, Ralph, additional, and Steinfeld, Robert, additional

Published
2022
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5. Organosilicon Radicals with Si–H and Si–Me Bonds from Commodity Precursors

Author

Kundu, Subrata, primary, Samuel, Prinson P., additional, Sinhababu, Soumen, additional, Luebben, Anna V., additional, Dittrich, Birger, additional, Andrada, Diego M., additional, Frenking, Gernot, additional, Stückl, A. Claudia, additional, Schwederski, Brigitte, additional, Paretzki, Alexa, additional, Kaim, Wolfgang, additional, and Roesky, Herbert W., additional

Published
2017
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6. Organosilicon Radicals with Si–H and Si–Me Bonds from Commodity Precursors

Author

Kundu, Subrata, Samuel, Prinson P., Sinhababu, Soumen, Luebben, Anna V., Dittrich, Birger, Andrada, Diego M., Frenking, Gernot, Stückl, A. Claudia, Schwederski, Brigitte, Paretzki, Alexa, Kaim, Wolfgang, and Roesky, Herbert W.

Abstract

The cyclic alkyl(amino) carbene (cAAC) stabilized biradicals of composition (cAAC)2SiH2(1), (cAAC)SiMe2-SiMe2(cAAC) (2), and (cAAC)SiMeCl-SiMeCl(cAAC) (3) have been isolated as molecular species. All the compounds are stable at room temperature for more than 6 months under inert conditions in the solid state. All radical species were fully characterized by single-crystal X-ray structure analysis and EPR spectroscopy. Furthermore, the structure and bonding of compounds 1–3have been investigated by theoretical methods. Compound 1contains the SiH2moiety and this is the first instance, where we have isolated 1without an acceptor molecule.

Published
2024
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9. Xen crystallography - choose your radiation

Author

Gruene, Tim, primary, Hahn, Hinrich W., additional, Luebben, Anna V., additional, Meilleur, Flora, additional, Sheldrick, George M., additional, Köpfer, David A., additional, Song, Chen, additional, Zachariae, Ulrich, additional, de Groot, Bert L., additional, and Luebben, Jens, additional

Published
2015
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12. Refinement of macromolecular structures against neutron data with SHELXL2013.

Author

Gruene, Tim, Hahn, Hinrich W., Luebben, Anna V., Meilleur, Flora, and Sheldrick, George M.

Subjects
MACROMOLECULES, NEUTRONS, GRAIN refinement, PROTEIN structure, SMALL molecules
Abstract

Some of the improvements in SHELX2013 make SHELXL convenient to use for refinement of macromolecular structures against neutron data without the support of X-ray data. The new NEUT instruction adjusts the behaviour of the SFAC instruction as well as the default bond lengths of the AFIX instructions. This work presents a protocol on how to use SHELXL for refinement of protein structures against neutron data. It includes restraints extending the Engh & Huber [Acta Cryst. (1991), A47, 392-400] restraints to H atoms and discusses several of the features of SHELXL that make the program particularly useful for the investigation of H atoms with neutron diffraction. SHELXL2013 is already adequate for the refinement of small molecules against neutron data, but there is still room for improvement, like the introduction of chain IDs for the refinement of macromolecular structures. [ABSTRACT FROM AUTHOR]

Published
2014
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13. Cln5 represents a new type of cysteine-based S -depalmitoylase linked to neurodegeneration.

Author

Luebben AV, Bender D, Becker S, Crowther LM, Erven I, Hofmann K, Söding J, Klemp H, Bellotti C, Stäuble A, Qiu T, Kathayat RS, Dickinson BC, Gärtner J, Sheldrick GM, Krätzner R, and Steinfeld R

Subjects
Child, Humans, Lysosomal Membrane Proteins genetics, Lysosomal Membrane Proteins metabolism, Membrane Proteins metabolism, Cysteine, Neuronal Ceroid-Lipofuscinoses genetics, Neuronal Ceroid-Lipofuscinoses metabolism
Abstract

Genetic CLN5 variants are associated with childhood neurodegeneration and Alzheimer's disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase ( S -depalmitoylation) activity using fluorescent substrates. Mutational analysis revealed that the predicted catalytic residues histidine-166 and cysteine-280 are critical for Cln5 thioesterase activity, uncovering a new cysteine-based catalytic mechanism for S -depalmitoylation enzymes. Last, we found that Cln5-deficient neuronal progenitor cells showed reduced thioesterase activity, confirming live cell function of Cln5 in setting S -depalmitoylation levels. Our results provide new insight into the function of Cln5, emphasize the importance of S -depalmitoylation in neuronal homeostasis, and disclose a new, unexpected enzymatic function for the N1pC/P60 superfamily of proteins.

Published
2022
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