Search

Your search keyword '"Ben-Zeev, Efrat"' showing total 35 results
Start Over Author "Ben-Zeev, Efrat"
35 results on '"Ben-Zeev, Efrat"'

2. Selective Assembly of Na,K-ATPase α2β2 Heterodimers in the Heart DISTINCT FUNCTIONAL PROPERTIES AND ISOFORM-SELECTIVE INHIBITORS*

Author

Habeck, Michael, Tokhtaeva, Elmira, Nadav, Yotam, Ben Zeev, Efrat, Ferris, Sean P, Kaufman, Randal J, Bab-Dinitz, Elizabeta, Kaplan, Jack H, Dada, Laura A, Farfel, Zvi, Tal, Daniel M, Katz, Adriana, Sachs, George, Vagin, Olga, and Karlish, Steven JD

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Heart Disease, Cardiovascular, Adenosine Triphosphatases, Animals, Cation Transport Proteins, Cell Adhesion Molecules, Neuronal, Dimerization, Enzyme Inhibitors, Humans, Isoenzymes, Kinetics, Mice, Myocardium, Potassium, Sodium, Sodium-Potassium-Exchanging ATPase, Na+/K+-ATPase, alpha2beta2, cardiomyocyte, excitation-contraction coupling, isoform assembly, isoform-selective inhibitors, kinetics, medicinal chemistry, molecular modeling, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

The Na,K-ATPase α2 subunit plays a key role in cardiac muscle contraction by regulating intracellular Ca2+, whereas α1 has a more conventional role of maintaining ion homeostasis. The β subunit differentially regulates maturation, trafficking, and activity of α-β heterodimers. It is not known whether the distinct role of α2 in the heart is related to selective assembly with a particular one of the three β isoforms. We show here by immunofluorescence and co-immunoprecipitation that α2 is preferentially expressed with β2 in T-tubules of cardiac myocytes, forming α2β2 heterodimers. We have expressed human α1β1, α2β1, α2β2, and α2β3 in Pichia pastoris, purified the complexes, and compared their functional properties. α2β2 and α2β3 differ significantly from both α2β1 and α1β1 in having a higher K0.5K+ and lower K0.5Na+ for activating Na,K-ATPase. These features are the result of a large reduction in binding affinity for extracellular K+ and shift of the E1P-E2P conformational equilibrium toward E1P. A screen of perhydro-1,4-oxazepine derivatives of digoxin identified several derivatives (e.g. cyclobutyl) with strongly increased selectivity for inhibition of α2β2 and α2β3 over α1β1 (range 22-33-fold). Molecular modeling suggests a possible basis for isoform selectivity. The preferential assembly, specific T-tubular localization, and low K+ affinity of α2β2 could allow an acute response to raised ambient K+ concentrations in physiological conditions and explain the importance of α2β2 for cardiac muscle contractility. The high sensitivity of α2β2 to digoxin derivatives explains beneficial effects of cardiac glycosides for treatment of heart failure and potential of α2β2-selective digoxin derivatives for reducing cardiotoxicity.

Published
2016

5. Reshaping Echinocandin Antifungal Drugs To Circumvent Glucan Synthase Point‐Mutation‐Mediated Resistance.

Author

Jospe‐Kaufman, Moriah, Ben‐Zeev, Efrat, Mottola, Austin, Dukhovny, Anna, Berman, Judith, Carmeli, Shmuel, and Fridman, Micha

Subjects
*GLUCAN synthase, *ECHINOCANDINS, *FUNGAL cell walls, *ANTIFUNGAL agents, *MEMBRANE lipids, *CHEMICAL resistance
Abstract

Echinocandins are a class of antifungal drugs that inhibit the activity of the β‐(1,3)‐glucan synthase complex, which synthesizes fungal cell wall β‐(1,3)‐glucan. Echinocandin resistance is linked to mutations in the FKS gene, which encodes the catalytic subunit of the glucan synthase complex. We present a molecular‐docking‐based model that provides insight into how echinocandins interact with the target Fks protein: echinocandins form a ternary complex with both Fks and membrane lipids. We used reductive dehydration of alcohols to generate dehydroxylated echinocandin derivatives and evaluated their potency against a panel of Candida pathogens constructed by introducing resistance‐conferring mutations in the FKS gene. We found that removing the hemiaminal alcohol, which drives significant conformational alterations in the modified echinocandins, reduced their efficacy. Conversely, eliminating the benzylic alcohol of echinocandins enhanced potency by up to two orders of magnitude, in a manner dependent upon the resistance‐conferring mutation. Strains that have developed resistance to either rezafungin, the most recently clinically approved echinocandin, or its dehydroxylated derivative RZF‐1, exhibit high resistance to rezafungin while demonstrating moderate resistance to RZF‐1. These findings provide valuable insight for combating echinocandin resistance through chemical modifications. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

6. Identification and characterization of the key enzyme in the biosynthesis of the neurotoxin β-ODAP in grass pea

Author

Goldsmith, Moshe, primary, Barad, Shiri, additional, Knafo, Maor, additional, Savidor, Alon, additional, Ben-Dor, Shifra, additional, Brandis, Alexander, additional, Mehlman, Tevie, additional, Peleg, Yoav, additional, Albeck, Shira, additional, Dym, Orly, additional, Ben-Zeev, Efrat, additional, Barbole, Ranjit S., additional, Aharoni, Asaph, additional, and Reich, Ziv, additional

Published
2022
Full Text
View/download PDF

10. Bringing BOS to light: Uncovering the key enzyme in the biosynthesis of the neurotoxin β-ODAP in Grass Pea (Lathyrus sativusL.)

Author

Goldsmith, Moshe, primary, Barad, Shiri, additional, Knafo, Maor, additional, Savidor, Alon, additional, Ben-Dor, Shifra, additional, Brandis, Alexander, additional, Mehlman, Tevie, additional, Peleg, Yoav, additional, Albeck, Shira, additional, Dym, Orly, additional, Ben-Zeev, Efrat, additional, and Reich, Ziv, additional

Published
2020
Full Text
View/download PDF

14. The mitochondrial carrier Citrin plays a role in regulating cellular energy during carcinogenesis

Author

Rabinovich, Shiran, primary, Silberman, Alon, additional, Adler, Lital, additional, Agron, Shani, additional, Levin-Zaidman, Smadar, additional, Bahat, Amir, additional, Porat, Ziv, additional, Ben-Zeev, Efrat, additional, Geva, Inbal, additional, Itkin, Maxim, additional, Malitsky, Sergey, additional, Buchaklian, Adam, additional, Helbling, Daniel, additional, Dimmock, David, additional, and Erez, Ayelet, additional

Published
2019
Full Text
View/download PDF

16. Prediction of homoprotein and heteroprotein complexes by protein docking and template-based modeling: A CASP-CAPRI experiment

Author

Lensink, Marc F., Velankar, Sameer, Kryshtafovych, Andriy, Huang, Shen You, Schneidman-Duhovny, Dina, Sali, Andrej, Segura, Joan, Fernandez-Fuentes, Narcis, Viswanath, Shruthi, Elber, Ron, Grudinin, Sergei, Popov, Petr, Neveu, Emilie, Lee, Hasup, Baek, Minkyung, Park, Sangwoo, Heo, Lim, Lee, Gyu Rie, Seok, Chaok, Qin, Sanbo, Zhou, Huan Xiang, Ritchie, David W., Maigret, Bernard, Devignes, Marie Dominique, Ghoorah, Anisah, Torchala, Mieczyslaw, Chaleil, Raphaël A.G., Bates, Paul A., Ben-Zeev, Efrat, Eisenstein, Miriam, Negi, Surendra S., Weng, Zhiping, Vreven, Thom, Pierce, Brian G., Borrman, Tyler M., Yu, Jinchao, Ochsenbein, Françoise, Guerois, Raphaël, Vangone, Anna, Rodrigues, João P.G.L.M., Van Zundert, Gydo, Nellen, Mehdi, Xue, Li, Karaca, Ezgi, Melquiond, Adrien S.J., Visscher, Koen, Kastritis, Panagiotis L., Bonvin, Alexandre M.J.J., Xu, Xianjin, Qiu, Liming, Yan, Chengfei, Li, Jilong, Ma, Zhiwei, Cheng, Jianlin, Zou, Xiaoqin, Shen, Yang, Peterson, Lenna X., Kim, Hyung Rae, Roy, Amit, Han, Xusi, Esquivel-Rodriguez, Juan, Kihara, Daisuke, Yu, Xiaofeng, Bruce, Neil J., Fuller, Jonathan C., Wade, Rebecca C., Anishchenko, Ivan, Kundrotas, Petras J., Vakser, Ilya A., Imai, Kenichiro, Yamada, Kazunori, Oda, Toshiyuki, Nakamura, Tsukasa, Tomii, Kentaro, Pallara, Chiara, Romero-Durana, Miguel, Jiménez-García, Brian, Moal, Iain H., Férnandez-Recio, Juan, Joung, Jong Young, Kim, Jong Yun, Joo, Keehyoung, Lee, Jooyoung, Kozakov, Dima, Vajda, Sandor, Mottarella, Scott, Hall, David R., Beglov, Dmitri, Mamonov, Artem, Xia, Bing, Bohnuud, Tanggis, Del Carpio, Carlos A., Ichiishi, Eichiro, Marze, Nicholas, Kuroda, Daisuke, Roy Burman, Shourya S., Gray, Jeffrey J., Chermak, Edrisse, Cavallo, Luigi, Oliva, Romina, Tovchigrechko, Andrey, Wodak, Shoshana J., Molecular and Computational Toxicology, and AIMMS

Subjects
Protein docking, CASP, Protein interaction, SDG 1 - No Poverty, Oligomer state, Blind prediction, CAPRI
Abstract

We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. Proteins 2016; 84(Suppl 1):323-348. © 2016 Wiley Periodicals, Inc.

Published
2016

18. Chiral Fluorescent Antifungal Azole Probes Detect Resistance, Uptake Dynamics, and Subcellular Distribution in CandidaSpecies

Author

Koren, Vlad, Ben-Zeev, Efrat, Voronov, Ivan, and Fridman, Micha

Abstract

Azoles are essential for fungal infection treatment, yet the increasing resistance highlights the need for innovative diagnostic tools and strategies to revitalize this class of antifungals. We developed two enantiomers of a fluorescent antifungal azole probe (1Sand 1R), analyzing 60 Candidastrains via live-cell microscopy. A database of azole distribution images in strains of Candida albicans, Candida glabrata, and Candida parapsilosis, among the most important pathogenic Candidaspecies, was established and analyzed. This analysis revealed distinct populations of yeast cells based on the correlation between fluorescent probe uptake and cell diameter. Varied uptake levels and subcellular distribution patterns were observed in C. albicans, C. glabrata, and C. parapsilosis, with the latter displaying increased localization to lipid droplets. Comparison of the more potent fluorescent antifungal azole probe enantiomer 1Swith the moderately potent enantiomer 1Rhighlighted time-dependent differences in the uptake profiles. The former displayed a marked elevation in uptake after approximately 150 min, indicating the time required for significant cell permeabilization to occur and its association with the azole’s antifungal activity potency. Divergent uptake levels between susceptible and high efflux-based azole-resistant strains were detected, offering a rapid diagnostic approach for identifying azole resistance. This study highlights unique insights achievable through fluorescent antifungal azole probes, unraveling the complexities of azole resistance, subcellular dynamics, and uptake within fungal pathogens.

Published
2024
Full Text
View/download PDF

19. Prediction of homoprotein and heteroprotein complexes by protein docking and template-based modeling: A CASP-CAPRI experiment

Author

NMR Spectroscopy, Sub NMR Spectroscopy, Lensink, Marc F., Velankar, Sameer, Kryshtafovych, Andriy, Huang, Shen You, Schneidman-Duhovny, Dina, Sali, Andrej, Segura, Joan, Fernandez-Fuentes, Narcis, Viswanath, Shruthi, Elber, Ron, Grudinin, Sergei, Popov, Petr, Neveu, Emilie, Lee, Hasup, Baek, Minkyung, Park, Sangwoo, Heo, Lim, Rie Lee, Gyu, Seok, Chaok, Qin, Sanbo, Zhou, Huan Xiang, Ritchie, David W., Maigret, Bernard, Devignes, Marie Dominique, Ghoorah, Anisah, Torchala, Mieczyslaw, Chaleil, Raphaël A G, Bates, Paul A., Ben-Zeev, Efrat, Eisenstein, Miriam, Negi, Surendra S., Weng, Zhiping, Vreven, Thom, Pierce, Brian G., Borrman, Tyler M., Yu, Jinchao, Ochsenbein, Françoise, Guerois, Raphaël, Vangone, Anna, Garcia Lopes Maia Rodrigues, João, van Zundert, Gydo, Nellen, Mehdi, Xue, Li, Karaca, Ezgi, Melquiond, Adrien S J, Visscher, Koen, Kastritis, Panagiotis L., Bonvin, Alexandre M J J, Xu, Xianjin, Qiu, Liming, Yan, Chengfei, Li, Jilong, Ma, Zhiwei, Cheng, Jianlin, Zou, Xiaoqin, Shen, Yang, Peterson, Lenna X., Kim, Hyung Rae, Roy, Amit, Han, Xusi, Esquivel-Rodriguez, Juan, Kihara, Daisuke, Yu, Xiaofeng, Bruce, Neil J., Fuller, Jonathan C., Wade, Rebecca C., Anishchenko, Ivan, Kundrotas, Petras J., Vakser, Ilya A., Imai, Kenichiro, Yamada, Kazunori, Oda, Toshiyuki, Nakamura, Tsukasa, Tomii, Kentaro, Pallara, Chiara, Romero-Durana, Miguel, Jiménez-García, Brian, Moal, Iain H., Férnandez-Recio, Juan, Joung, Jong Young, Kim, Jong Yun, Joo, Keehyoung, Lee, Jooyoung, Kozakov, Dima, Vajda, Sandor, Mottarella, Scott, Hall, David R., Beglov, Dmitri, Mamonov, Artem, Xia, Bing, Bohnuud, Tanggis, Del Carpio, Carlos A., Ichiishi, Eichiro, Marze, Nicholas, Kuroda, Daisuke, Roy Burman, Shourya S., Gray, Jeffrey J., Chermak, Edrisse, Cavallo, Luigi, Oliva, Romina, Tovchigrechko, Andrey, Wodak, Shoshana J., NMR Spectroscopy, Sub NMR Spectroscopy, Lensink, Marc F., Velankar, Sameer, Kryshtafovych, Andriy, Huang, Shen You, Schneidman-Duhovny, Dina, Sali, Andrej, Segura, Joan, Fernandez-Fuentes, Narcis, Viswanath, Shruthi, Elber, Ron, Grudinin, Sergei, Popov, Petr, Neveu, Emilie, Lee, Hasup, Baek, Minkyung, Park, Sangwoo, Heo, Lim, Rie Lee, Gyu, Seok, Chaok, Qin, Sanbo, Zhou, Huan Xiang, Ritchie, David W., Maigret, Bernard, Devignes, Marie Dominique, Ghoorah, Anisah, Torchala, Mieczyslaw, Chaleil, Raphaël A G, Bates, Paul A., Ben-Zeev, Efrat, Eisenstein, Miriam, Negi, Surendra S., Weng, Zhiping, Vreven, Thom, Pierce, Brian G., Borrman, Tyler M., Yu, Jinchao, Ochsenbein, Françoise, Guerois, Raphaël, Vangone, Anna, Garcia Lopes Maia Rodrigues, João, van Zundert, Gydo, Nellen, Mehdi, Xue, Li, Karaca, Ezgi, Melquiond, Adrien S J, Visscher, Koen, Kastritis, Panagiotis L., Bonvin, Alexandre M J J, Xu, Xianjin, Qiu, Liming, Yan, Chengfei, Li, Jilong, Ma, Zhiwei, Cheng, Jianlin, Zou, Xiaoqin, Shen, Yang, Peterson, Lenna X., Kim, Hyung Rae, Roy, Amit, Han, Xusi, Esquivel-Rodriguez, Juan, Kihara, Daisuke, Yu, Xiaofeng, Bruce, Neil J., Fuller, Jonathan C., Wade, Rebecca C., Anishchenko, Ivan, Kundrotas, Petras J., Vakser, Ilya A., Imai, Kenichiro, Yamada, Kazunori, Oda, Toshiyuki, Nakamura, Tsukasa, Tomii, Kentaro, Pallara, Chiara, Romero-Durana, Miguel, Jiménez-García, Brian, Moal, Iain H., Férnandez-Recio, Juan, Joung, Jong Young, Kim, Jong Yun, Joo, Keehyoung, Lee, Jooyoung, Kozakov, Dima, Vajda, Sandor, Mottarella, Scott, Hall, David R., Beglov, Dmitri, Mamonov, Artem, Xia, Bing, Bohnuud, Tanggis, Del Carpio, Carlos A., Ichiishi, Eichiro, Marze, Nicholas, Kuroda, Daisuke, Roy Burman, Shourya S., Gray, Jeffrey J., Chermak, Edrisse, Cavallo, Luigi, Oliva, Romina, Tovchigrechko, Andrey, and Wodak, Shoshana J.

Published
2016

20. Prediction of homoprotein and heteroprotein complexes by protein docking and template-based modeling: A CASP-CAPRI experiment.

Author

Lensink, Marc, Lensink, Marc, Velankar, Sameer, Kryshtafovych, Andriy, Huang, Shen-You, Schneidman-Duhovny, Dina, Sali, Andrej, Segura, Joan, Fernandez-Fuentes, Narcis, Viswanath, Shruthi, Elber, Ron, Grudinin, Sergei, Popov, Petr, Neveu, Emilie, Lee, Hasup, Baek, Minkyung, Park, Sangwoo, Heo, Lim, Rie Lee, Gyu, Seok, Chaok, Qin, Sanbo, Zhou, Huan-Xiang, Ritchie, David, Maigret, Bernard, Devignes, Marie-Dominique, Ghoorah, Anisah, Torchala, Mieczyslaw, Chaleil, Raphaël, Bates, Paul, Ben-Zeev, Efrat, Eisenstein, Miriam, Negi, Surendra, Weng, Zhiping, Vreven, Thom, Pierce, Brian, Borrman, Tyler, Yu, Jinchao, Ochsenbein, Françoise, Guerois, Raphaël, Vangone, Anna, Rodrigues, João, van Zundert, Gydo, Nellen, Mehdi, Xue, Li, Karaca, Ezgi, Melquiond, Adrien, Visscher, Koen, Kastritis, Panagiotis, Bonvin, Alexandre, Xu, Xianjin, Qiu, Liming, Yan, Chengfei, Li, Jilong, Ma, Zhiwei, Cheng, Jianlin, Zou, Xiaoqin, Shen, Yang, Peterson, Lenna, Kim, Hyung-Rae, Roy, Amit, Han, Xusi, Esquivel-Rodriguez, Juan, Kihara, Daisuke, Yu, Xiaofeng, Bruce, Neil, Fuller, Jonathan, Wade, Rebecca, Anishchenko, Ivan, Kundrotas, Petras, Vakser, Ilya, Imai, Kenichiro, Yamada, Kazunori, Oda, Toshiyuki, Nakamura, Tsukasa, Tomii, Kentaro, Pallara, Chiara, Romero-Durana, Miguel, Jiménez-García, Brian, Moal, Iain, Férnandez-Recio, Juan, Joung, Jong, Kim, Jong, Joo, Keehyoung, Lee, Jooyoung, Kozakov, Dima, Vajda, Sandor, Mottarella, Scott, Hall, David, Beglov, Dmitri, Mamonov, Artem, Xia, Bing, Bohnuud, Tanggis, Del Carpio, Carlos, Ichiishi, Eichiro, Marze, Nicholas, Kuroda, Daisuke, Roy Burman, Shourya, Gray, Jeffrey, Chermak, Edrisse, Cavallo, Luigi, Lensink, Marc, Lensink, Marc, Velankar, Sameer, Kryshtafovych, Andriy, Huang, Shen-You, Schneidman-Duhovny, Dina, Sali, Andrej, Segura, Joan, Fernandez-Fuentes, Narcis, Viswanath, Shruthi, Elber, Ron, Grudinin, Sergei, Popov, Petr, Neveu, Emilie, Lee, Hasup, Baek, Minkyung, Park, Sangwoo, Heo, Lim, Rie Lee, Gyu, Seok, Chaok, Qin, Sanbo, Zhou, Huan-Xiang, Ritchie, David, Maigret, Bernard, Devignes, Marie-Dominique, Ghoorah, Anisah, Torchala, Mieczyslaw, Chaleil, Raphaël, Bates, Paul, Ben-Zeev, Efrat, Eisenstein, Miriam, Negi, Surendra, Weng, Zhiping, Vreven, Thom, Pierce, Brian, Borrman, Tyler, Yu, Jinchao, Ochsenbein, Françoise, Guerois, Raphaël, Vangone, Anna, Rodrigues, João, van Zundert, Gydo, Nellen, Mehdi, Xue, Li, Karaca, Ezgi, Melquiond, Adrien, Visscher, Koen, Kastritis, Panagiotis, Bonvin, Alexandre, Xu, Xianjin, Qiu, Liming, Yan, Chengfei, Li, Jilong, Ma, Zhiwei, Cheng, Jianlin, Zou, Xiaoqin, Shen, Yang, Peterson, Lenna, Kim, Hyung-Rae, Roy, Amit, Han, Xusi, Esquivel-Rodriguez, Juan, Kihara, Daisuke, Yu, Xiaofeng, Bruce, Neil, Fuller, Jonathan, Wade, Rebecca, Anishchenko, Ivan, Kundrotas, Petras, Vakser, Ilya, Imai, Kenichiro, Yamada, Kazunori, Oda, Toshiyuki, Nakamura, Tsukasa, Tomii, Kentaro, Pallara, Chiara, Romero-Durana, Miguel, Jiménez-García, Brian, Moal, Iain, Férnandez-Recio, Juan, Joung, Jong, Kim, Jong, Joo, Keehyoung, Lee, Jooyoung, Kozakov, Dima, Vajda, Sandor, Mottarella, Scott, Hall, David, Beglov, Dmitri, Mamonov, Artem, Xia, Bing, Bohnuud, Tanggis, Del Carpio, Carlos, Ichiishi, Eichiro, Marze, Nicholas, Kuroda, Daisuke, Roy Burman, Shourya, Gray, Jeffrey, Chermak, Edrisse, and Cavallo, Luigi

Abstract

We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. Proteins 2016; 84(Suppl 1):323-348. © 2016 Wiley Periodicals, Inc.

Published
2016

21. Prediction of homoprotein and heteroprotein complexes by protein docking and template-based modeling: A CASP-CAPRI experiment

Author

Barcelona Supercomputing Center, Lesink, Marc F., Velankar, Sameer, Kryshtafovych, Andriy, Huang, Shen-You, Schneidman-Duhovny, Dina, Sali, Andrej, Segura, Joan, Fernandez-Fuentes, Narcis, Shruthi, Viswanath, Elber, Ron, Grudinin, Sergei, Popov, Petr, Neveu, Emilie, Lee, Hasup, Baek, Minkyung, Park, Sangwoo, Heo, Lim, Lee, Gyu R., Seok, Chaok, Qin, Sanbo, Zhou, Huan-Xiang, Ritchie, David W., Maigret, Bernard, Devignes, Marie-Dominique, Ghoorah, Anisah, Torchala, Mieczyslaw, Chaleil, Raphaël A.G., Bates, Paul A., Ben-Zeev, Efrat, Eisenstein, Miriam, Negi, Surendra S., Weng, Zhiping, Vreven, Thom, Pierce, Brian G., Borrman, Tyler M., Yu, Jinchao, Ochsenbein, Françoise, Guerois, Raphaël, Vangone, Anna, Rodrigues, Joao P.G.L.M., Zundert, Gydo van, Nellen, Mehdi, Xue, Li, Karaca, Ezgi, Melquiond, Adrien S.J., Visscher, Koen, Kastritis, Panagiotis L., Bonvin, Alexandre M.J.J., Xianjin, Xu, Qiu, Liming, Yan, Chengfei, Li, Jilong, Ma, Zhiwei, Cheng, Jianlin, Zou, Xiaoqin, Shen, Yang, Peterson, Lenna X., Kim, Hyung-Rae, Roy, Amit, Han, Xusi, Esquivel-Rodriguez, Juan, Kihara, Daisuke, Yu, Xiaofeng, Bruce, Neil J., Fuller, Jonathan C., Wade, Rebecca C., Anishchenko, Ivan, Kundrotas, Petras J., Vakser, Ilya A., Imai, Kenichiro, Yamada, Kazunori, Oda, Toshiyuki, Nakamura, Tsukasa, Tomii, Kentaro, Pallara, Chiara, Romero-Durana, Miguel, Jiménez-García, Brian, Moal, Iain H., Fernández-Recio, Juan, Joung, Jong Y., Kim, Jong Y., Joo, Keehyoung, Lee, Jooyoung, Kozakov, Dima, Vajda, Sandor, Mottarella, Scott, Hall, David R., Beglov, Dmitri, Mamonov, Artem, Xia, Bing, Bohnuud, Tanggis, del Carpio, Carlos A., Ichiishi, Eichiro, Marze, Nicholas, Kuroda, Daisuke, Burman, Shourya S., Gray, Jeffrey J., Chermak, Edrisse, Cavallo, Luigi, Oliva, Romina, Tovchigrechko, Andrey, Wodak, Shoshana J., Barcelona Supercomputing Center, Lesink, Marc F., Velankar, Sameer, Kryshtafovych, Andriy, Huang, Shen-You, Schneidman-Duhovny, Dina, Sali, Andrej, Segura, Joan, Fernandez-Fuentes, Narcis, Shruthi, Viswanath, Elber, Ron, Grudinin, Sergei, Popov, Petr, Neveu, Emilie, Lee, Hasup, Baek, Minkyung, Park, Sangwoo, Heo, Lim, Lee, Gyu R., Seok, Chaok, Qin, Sanbo, Zhou, Huan-Xiang, Ritchie, David W., Maigret, Bernard, Devignes, Marie-Dominique, Ghoorah, Anisah, Torchala, Mieczyslaw, Chaleil, Raphaël A.G., Bates, Paul A., Ben-Zeev, Efrat, Eisenstein, Miriam, Negi, Surendra S., Weng, Zhiping, Vreven, Thom, Pierce, Brian G., Borrman, Tyler M., Yu, Jinchao, Ochsenbein, Françoise, Guerois, Raphaël, Vangone, Anna, Rodrigues, Joao P.G.L.M., Zundert, Gydo van, Nellen, Mehdi, Xue, Li, Karaca, Ezgi, Melquiond, Adrien S.J., Visscher, Koen, Kastritis, Panagiotis L., Bonvin, Alexandre M.J.J., Xianjin, Xu, Qiu, Liming, Yan, Chengfei, Li, Jilong, Ma, Zhiwei, Cheng, Jianlin, Zou, Xiaoqin, Shen, Yang, Peterson, Lenna X., Kim, Hyung-Rae, Roy, Amit, Han, Xusi, Esquivel-Rodriguez, Juan, Kihara, Daisuke, Yu, Xiaofeng, Bruce, Neil J., Fuller, Jonathan C., Wade, Rebecca C., Anishchenko, Ivan, Kundrotas, Petras J., Vakser, Ilya A., Imai, Kenichiro, Yamada, Kazunori, Oda, Toshiyuki, Nakamura, Tsukasa, Tomii, Kentaro, Pallara, Chiara, Romero-Durana, Miguel, Jiménez-García, Brian, Moal, Iain H., Fernández-Recio, Juan, Joung, Jong Y., Kim, Jong Y., Joo, Keehyoung, Lee, Jooyoung, Kozakov, Dima, Vajda, Sandor, Mottarella, Scott, Hall, David R., Beglov, Dmitri, Mamonov, Artem, Xia, Bing, Bohnuud, Tanggis, del Carpio, Carlos A., Ichiishi, Eichiro, Marze, Nicholas, Kuroda, Daisuke, Burman, Shourya S., Gray, Jeffrey J., Chermak, Edrisse, Cavallo, Luigi, Oliva, Romina, Tovchigrechko, Andrey, and Wodak, Shoshana J.

Abstract

We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein–protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy., We are most grateful to the PDBe at the European Bioinformatics Institute in Hinxton, UK, for hosting the CAPRI website. Our deepest thanks go to all the structural biologists and to the following structural genomics initiatives: Northeast Structural Genomics Consortium, Joint Center for Structural Genomics, NatPro PSI:Biology, New York Structural Genomics Research Center, Midwest Center for Structural Genomics, Structural Genomics Consortium, for contributing the targets for this joint CASP-CAPRI experiment. MFL acknowledges support from the FRABio FR3688 Research Federation “Structural & Functional Biochemistry of Biomolecular Assemblies.”, Peer Reviewed, Postprint (published version)

Published
2016

22. Prediction of homoprotein and heteroprotein complexes by protein docking and template‐based modeling: A CASP‐CAPRI experiment

Author

Lensink, Marc F., primary, Velankar, Sameer, additional, Kryshtafovych, Andriy, additional, Huang, Shen‐You, additional, Schneidman‐Duhovny, Dina, additional, Sali, Andrej, additional, Segura, Joan, additional, Fernandez‐Fuentes, Narcis, additional, Viswanath, Shruthi, additional, Elber, Ron, additional, Grudinin, Sergei, additional, Popov, Petr, additional, Neveu, Emilie, additional, Lee, Hasup, additional, Baek, Minkyung, additional, Park, Sangwoo, additional, Heo, Lim, additional, Rie Lee, Gyu, additional, Seok, Chaok, additional, Qin, Sanbo, additional, Zhou, Huan‐Xiang, additional, Ritchie, David W., additional, Maigret, Bernard, additional, Devignes, Marie‐Dominique, additional, Ghoorah, Anisah, additional, Torchala, Mieczyslaw, additional, Chaleil, Raphaël A.G., additional, Bates, Paul A., additional, Ben‐Zeev, Efrat, additional, Eisenstein, Miriam, additional, Negi, Surendra S., additional, Weng, Zhiping, additional, Vreven, Thom, additional, Pierce, Brian G., additional, Borrman, Tyler M., additional, Yu, Jinchao, additional, Ochsenbein, Françoise, additional, Guerois, Raphaël, additional, Vangone, Anna, additional, Rodrigues, João P.G.L.M., additional, van Zundert, Gydo, additional, Nellen, Mehdi, additional, Xue, Li, additional, Karaca, Ezgi, additional, Melquiond, Adrien S.J., additional, Visscher, Koen, additional, Kastritis, Panagiotis L., additional, Bonvin, Alexandre M.J.J., additional, Xu, Xianjin, additional, Qiu, Liming, additional, Yan, Chengfei, additional, Li, Jilong, additional, Ma, Zhiwei, additional, Cheng, Jianlin, additional, Zou, Xiaoqin, additional, Shen, Yang, additional, Peterson, Lenna X., additional, Kim, Hyung‐Rae, additional, Roy, Amit, additional, Han, Xusi, additional, Esquivel‐Rodriguez, Juan, additional, Kihara, Daisuke, additional, Yu, Xiaofeng, additional, Bruce, Neil J., additional, Fuller, Jonathan C., additional, Wade, Rebecca C., additional, Anishchenko, Ivan, additional, Kundrotas, Petras J., additional, Vakser, Ilya A., additional, Imai, Kenichiro, additional, Yamada, Kazunori, additional, Oda, Toshiyuki, additional, Nakamura, Tsukasa, additional, Tomii, Kentaro, additional, Pallara, Chiara, additional, Romero‐Durana, Miguel, additional, Jiménez‐García, Brian, additional, Moal, Iain H., additional, Férnandez‐Recio, Juan, additional, Joung, Jong Young, additional, Kim, Jong Yun, additional, Joo, Keehyoung, additional, Lee, Jooyoung, additional, Kozakov, Dima, additional, Vajda, Sandor, additional, Mottarella, Scott, additional, Hall, David R., additional, Beglov, Dmitri, additional, Mamonov, Artem, additional, Xia, Bing, additional, Bohnuud, Tanggis, additional, Del Carpio, Carlos A., additional, Ichiishi, Eichiro, additional, Marze, Nicholas, additional, Kuroda, Daisuke, additional, Roy Burman, Shourya S., additional, Gray, Jeffrey J., additional, Chermak, Edrisse, additional, Cavallo, Luigi, additional, Oliva, Romina, additional, Tovchigrechko, Andrey, additional, and Wodak, Shoshana J., additional

Published
2016
Full Text
View/download PDF

27. Digoxin derivatives with selectivity for the a2ß3 isoform of Na,K-ATPase potently reduce intraocular pressure.

Author

Katz, Adriana, Tal, Daniel M., Heller, Dan, Habeck, Michael, Ben Zeev, Efrat, Rabah, Bilal, Bar Kana, Yaniv, Marcovich, Arie L., and Karlish, Steven J. D.

Subjects
ADENOSINE triphosphatase, DIGOXIN, INTRAOCULAR pressure, EPITHELIAL cells, GLAUCOMA treatment
Abstract

The ciliary epithelium in the eye consists of pigmented epithelial cells that express the a1ß1 isoform of Na,K-ATPase and nonpigmented epithelial cells that express mainly the a2ß3 isoform. In principle, a Na,K-ATPase inhibitor with selectivity for a2ß3 that penetrates the cornea could effectively reduce intraocular pressure, with minimal systemic or local toxicity. We have recently synthesized perhydro-1,4-oxazepine derivatives of digoxin by NaIO4 oxidation of the third digitoxose and reductive amination with various R-NH2 substituents and identified derivatives with significant selectivity for human a2ß1 over a1ß1 (up to 7.5-fold). When applied topically, the most a2-selective derivatives effectively prevented or reversed pharmacologically raised intraocular pressure in rabbits. A recent structure of Na,K-ATPase, with bound digoxin, shows the third digitoxose approaching one residue in the ß1 subunit, Gln84, suggesting a role for ß in digoxin binding. Gln84 in ß1 is replaced by Val88 in ß3. Assuming that alkyl substituents might interact with ß3Val88, we synthesized perhydro-1,4-oxazepine derivatives of digoxin with diverse alkyl substituents. The methylcyclopropyl and cyclobutyl derivatives are strongly selective for a2ß3 over a1ß1 (22-33-fold respectively), as determined either with purified human isoform proteins or intact bovine nonpigmented epithelium cells. When applied topically on rabbit eyes, these derivatives potently reduce both pharmacologically raised and basal intraocular pressure. The cyclobutyl derivative is more efficient than Latanoprost, the most widely used glaucoma drug. Thus, the conclusion is that a2ß3-selective digoxin derivatives effectively penetrate the cornea and inhibit the Na,K-ATPase, hence reducing aqueous humor production. The new digoxin derivatives may have potential for glaucoma drug therapy. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

33. On the interaction of colicin E3 with the ribosome

Author

Zarivach, Raz, primary, Ben-Zeev, Efrat, additional, Wu, Nan, additional, Auerbach, Tamar, additional, Bashan, Anat, additional, Jakes, Karen, additional, Dickman, Katherine, additional, Kosmidis, Alexander, additional, Schluenzen, Frank, additional, Yonath, Ada, additional, Eisenstein, Miriam, additional, and Shoham, Menachem, additional

Published
2002
Full Text
View/download PDF

35. Phylogeny and abiotic conditions shape the diel floral emission patterns of desert Brassicaceae species.

Author

Cna'ani A, Dener E, Ben-Zeev E, Günther J, Köllner TG, Tzin V, and Seifan M

Subjects
Animals, Brassicaceae genetics, Darkness, Desert Climate, Flowers chemistry, Gas Chromatography-Mass Spectrometry, Insecta, Israel, Light, Plant Proteins genetics, Pollination, Ribosomal Proteins genetics, Volatile Organic Compounds analysis, Brassicaceae chemistry, Brassicaceae physiology, Flowers physiology, Phylogeny, Volatile Organic Compounds metabolism
Abstract

A key facet of floral scent is diel fluctuations in emission, often studied in the context of plant-pollinator interactions, while contributions of environment and phylogeny remain overlooked. Here, we ask if these factors are involved in shaping temporal variations in scent emission. To that end, we coupled light/dark floral emission measurements of 17 desert Brassicaceae species with environmental and phylogenetic data to explore the individual/combined impacts of these predictors on diel emission patterns. We further investigated these patterns by conducting high-resolution emission measurements in a subset of genetically distant species with contrasting temporal dynamics. While diel shifts in magnitude and richness of emission were strongly affected by genetic relatedness, they also reflect the environmental conditions under which the species grow. Specifically, light/dark emission ratios were negatively affected by an increase in winter temperatures, known to impact both plant physiology and insect locomotion, and sandy soil fractions, previously shown to exert stress that tempers with diel metabolic rhythms. Additionally, the biosynthetic origins of the compounds were associated with their corresponding production patterns, possibly to maximize emission efficacy. Using a multidisciplinary chemical/ecological approach, we uncover and differentiate the main factors shaping floral scent diel fluctuations, highlighting their consequences under changing global climate., (© 2021 John Wiley & Sons Ltd.)

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results