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Your search keyword '"Karpowich, Nathan K."' showing total 21 results
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21 results on '"Karpowich, Nathan K."'

2. Development of small molecule inhibitors of natural killer group 2D receptor (NKG2D)

Author

Wang, Jocelyn, primary, Nakafuku, Kohki M., additional, Ziff, Jeannie, additional, Gelin, Christine F., additional, Gholami, Hadi, additional, Thompson, Aaron A., additional, Karpowich, Nathan K., additional, Limon, Luis, additional, Coate, Heather R., additional, Damm-Ganamet, Kelly L., additional, Shih, Amy Y., additional, Grant, Joanna C., additional, Côte, Marjorie, additional, Mak, Puiying A., additional, Pascual, Heather A., additional, Rives, Marie-Laure, additional, Edwards, James P., additional, Venable, Jennifer D., additional, Venkatesan, Hariharan, additional, Shi, Zhicai, additional, Allen, Samantha J., additional, Sharma, Sujata, additional, Kung, Pei-Pei, additional, and Shireman, Brock T., additional

Published
2023
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3. Identification of small-molecule protein–protein interaction inhibitors for NKG2D

Author

Thompson, Aaron A., primary, Harbut, Michael B., additional, Kung, Pei-Pei, additional, Karpowich, Nathan K., additional, Branson, Jeffrey D., additional, Grant, Joanna C., additional, Hagan, Deborah, additional, Pascual, Heather A., additional, Bai, Guoyun, additional, Zavareh, Reza Beheshti, additional, Coate, Heather R., additional, Collins, Bernard C., additional, Côte, Marjorie, additional, Gelin, Christine F., additional, Damm-Ganamet, Kelly L., additional, Gholami, Hadi, additional, Huff, Adam R., additional, Limon, Luis, additional, Lumb, Kevin J., additional, Mak, Puiying A., additional, Nakafuku, Kohki M., additional, Price, Edmund V., additional, Shih, Amy Y., additional, Tootoonchi, Mandana, additional, Vellore, Nadeem A., additional, Wang, Jocelyn, additional, Wei, Na, additional, Ziff, Jeannie, additional, Berger, Scott B., additional, Edwards, James P., additional, Gardet, Agnès, additional, Sun, Siquan, additional, Towne, Jennifer E., additional, Venable, Jennifer D., additional, Shi, Zhicai, additional, Venkatesan, Hariharan, additional, Rives, Marie-Laure, additional, Sharma, Sujata, additional, Shireman, Brock T., additional, and Allen, Samantha J., additional

Published
2023
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13. Biophysics: Transporter in the spotlight

Author

Karpowich, Nathan K. and Wang, Da-Neng

Subjects
Models, Molecular, Alanine, Protein Conformation, Sodium, food and beverages, Molecular Dynamics Simulation, Crystallography, X-Ray, Plasma Membrane Neurotransmitter Transport Proteins, Article, Allosteric Regulation, Bacterial Proteins, Leucine, Escherichia coli, Fluorescence Resonance Energy Transfer, Aquifoliaceae, Cysteine
Abstract

Neurotransmitter:Na(+) symporters (NSS) remove neurotransmitters from the synapse in a reuptake process that is driven by the Na(+) gradient. Drugs that interfere with this reuptake mechanism, such as cocaine and antidepressants, profoundly influence behaviour and mood. To probe the nature of the conformational changes that are associated with substrate binding and transport, we have developed a single-molecule fluorescence imaging assay and combined it with functional and computational studies of the prokaryotic NSS homologue LeuT. Here we show molecular details of the modulation of intracellular gating of LeuT by substrates and inhibitors, as well as by mutations that alter binding, transport or both. Our direct observations of single-molecule transitions, reflecting structural dynamics of the intracellular region of the transporter that might be masked by ensemble averaging or suppressed under crystallographic conditions, are interpreted in the context of an allosteric mechanism that couples ion and substrate binding to transport.

Published
2010

20. LeuT-Desipramine Structure Reveals How Antidepressants Block Neurotransmitter Reuptake.

Author

Zheng Zhou, Zhen, Juan, Karpowich, Nathan K., Goetz, Regina M., Law, Christopher J., Reith, Maarten E. A., and Da-Neng Wang

Subjects
*ANTIDEPRESSANTS, *SEROTONIN, *DOPAMINE, *NORADRENALINE, *MUTAGENESIS, *LEUCINE
Abstract

Tricyclic antidepressants exert their pharmacological effect-inhibiting the reuptake of serotonin, norepinephrine, and dopamine—by directly blocking neurotransmitter transporters (SERT, NET, and DAT, respectively) in the presynaptic membrane. The drug-binding site and the mechanism of this inhibition are poorly understood. We determined the crystal structure at 2.9 angstroms of the bacterial leucine transporter (LeuT), a homolog of SERT, NET, and DAT, in complex with leucine and the antidepressant desipramine. Desipramine binds at the inner end of the extracellular cavity of the transporter and is held in place by a hairpin loop and by a salt bridge. This binding site is separated from the leucine-binding site by the extracellular gate of the transporter. By directly locking the gate, desipramine prevents conformational changes and blocks substrate transport. Mutagenesis experiments on human SERT and DAT indicate that both the desipramine-binding site and its inhibition mechanism are probably conserved in the human neurotransmitter transporters. [ABSTRACT FROM AUTHOR]

Published
2007
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21. Biophysics: Transporter in the spotlight.

Author

Karpowich NK and Wang DN

Subjects
Crystallography, X-Ray, Fluorescence Resonance Energy Transfer, Molecular Dynamics Simulation, Protein Conformation, Sodium metabolism, Bacterial Proteins chemistry, Bacterial Proteins metabolism, Plasma Membrane Neurotransmitter Transport Proteins chemistry, Plasma Membrane Neurotransmitter Transport Proteins metabolism
Published
2010
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