HSP90 interacts with the fibronectin N-terminal domains and increases matrix formation:
- Chakraborty, Abir, Boel, Natasha M-E, Edkins, Adrienne L
- Authors: Chakraborty, Abir , Boel, Natasha M-E , Edkins, Adrienne L
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165407 , vital:41241 , https://doi.org/10.3390/cells9020272
- Description: Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that controls the function and stability of a wide range of cellular client proteins. Fibronectin (FN) is an extracellular client protein of HSP90, and exogenous HSP90 or inhibitors of HSP90 alter the morphology of the extracellular matrix. Here, we further characterized the HSP90 and FN interaction. FN bound to the M domain of HSP90 and interacted with both the open and closed HSP90 conformations; and the interaction was reduced in the presence of sodium molybdate. HSP90 interacted with the N-terminal regions of FN, which are known to be important for matrix assembly.
- Full Text:
- Date Issued: 2020
- Authors: Chakraborty, Abir , Boel, Natasha M-E , Edkins, Adrienne L
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165407 , vital:41241 , https://doi.org/10.3390/cells9020272
- Description: Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that controls the function and stability of a wide range of cellular client proteins. Fibronectin (FN) is an extracellular client protein of HSP90, and exogenous HSP90 or inhibitors of HSP90 alter the morphology of the extracellular matrix. Here, we further characterized the HSP90 and FN interaction. FN bound to the M domain of HSP90 and interacted with both the open and closed HSP90 conformations; and the interaction was reduced in the presence of sodium molybdate. HSP90 interacted with the N-terminal regions of FN, which are known to be important for matrix assembly.
- Full Text:
- Date Issued: 2020
Integrated computational approaches and tools for allosteric drug discovery:
- Amamuddy, Olivier S, Veldman, Wade, Manyumwa, Colleen, Khairallah, Afrah, Agajanian, Steve, Oluyemi, Odeyemi, Verkhivker, Gennady M, Tastan Bishop, Özlem
- Authors: Amamuddy, Olivier S , Veldman, Wade , Manyumwa, Colleen , Khairallah, Afrah , Agajanian, Steve , Oluyemi, Odeyemi , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163012 , vital:41004 , https://doi.org/10.3390/ijms21030847
- Description: Understanding molecular mechanisms underlying the complexity of allosteric regulation in proteins has attracted considerable attention in drug discovery due to the benefits and versatility of allosteric modulators in providing desirable selectivity against protein targets while minimizing toxicity and other side effects. The proliferation of novel computational approaches for predicting ligand–protein interactions and binding using dynamic and network-centric perspectives has led to new insights into allosteric mechanisms and facilitated computer-based discovery of allosteric drugs. Although no absolute method of experimental and in silico allosteric drug/site discovery exists, current methods are still being improved. As such, the critical analysis and integration of established approaches into robust, reproducible, and customizable computational pipelines with experimental feedback could make allosteric drug discovery more efficient and reliable. In this article, we review computational approaches for allosteric drug discovery and discuss how these tools can be utilized to develop consensus workflows for in silico identification of allosteric sites and modulators with some applications to pathogen resistance and precision medicine. The emerging realization that allosteric modulators can exploit distinct regulatory mechanisms and can provide access to targeted modulation of protein activities could open opportunities for probing biological processes and in silico design of drug combinations with improved therapeutic indices and a broad range of activities.
- Full Text:
- Date Issued: 2020
- Authors: Amamuddy, Olivier S , Veldman, Wade , Manyumwa, Colleen , Khairallah, Afrah , Agajanian, Steve , Oluyemi, Odeyemi , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163012 , vital:41004 , https://doi.org/10.3390/ijms21030847
- Description: Understanding molecular mechanisms underlying the complexity of allosteric regulation in proteins has attracted considerable attention in drug discovery due to the benefits and versatility of allosteric modulators in providing desirable selectivity against protein targets while minimizing toxicity and other side effects. The proliferation of novel computational approaches for predicting ligand–protein interactions and binding using dynamic and network-centric perspectives has led to new insights into allosteric mechanisms and facilitated computer-based discovery of allosteric drugs. Although no absolute method of experimental and in silico allosteric drug/site discovery exists, current methods are still being improved. As such, the critical analysis and integration of established approaches into robust, reproducible, and customizable computational pipelines with experimental feedback could make allosteric drug discovery more efficient and reliable. In this article, we review computational approaches for allosteric drug discovery and discuss how these tools can be utilized to develop consensus workflows for in silico identification of allosteric sites and modulators with some applications to pathogen resistance and precision medicine. The emerging realization that allosteric modulators can exploit distinct regulatory mechanisms and can provide access to targeted modulation of protein activities could open opportunities for probing biological processes and in silico design of drug combinations with improved therapeutic indices and a broad range of activities.
- Full Text:
- Date Issued: 2020
In Search of the “Goodlife": Border Crossing and Agency in Luis Alberto Urrea's Into the Beautiful North and Graciela Limón's The River Flows North
- Authors: Naidu, Samantha
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/158046 , vital:40142 , https://doi.org/10.1080/18125441.2019.16474490
- Description: This article explores representations of complex diasporic subjectivities that resist, or attempt to resist, obsolete nationalist notions of citizenship and identity by crossing the US– Mexico border (and, in so doing, crossing other intangible borders) in search of a better life. Two examples of border literature, Luis Alberto Urrea's Into the Beautiful North (2009) and Graciela Limón's The River Flows North (2009), have been selected for analysis. These texts, in describing various diaspora spaces—to enlist Avtar Brah's term (Cartographies of Diaspora. London: Routledge, 1996)—also examine how those who do not migrate are affected by migration. In Writing the Goodlife: Mexican American Literature and the Environment (Tucson: University of Arizona Press, 2016), Priscilla Solis Ybarra reveals how the past century and a half's Mexican-American literature contains valuable new approaches to creating and sustaining new forms of transnational relations between humans, and ecologically sound relationships between humans and nature.
- Full Text:
- Date Issued: 2019
- Authors: Naidu, Samantha
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/158046 , vital:40142 , https://doi.org/10.1080/18125441.2019.16474490
- Description: This article explores representations of complex diasporic subjectivities that resist, or attempt to resist, obsolete nationalist notions of citizenship and identity by crossing the US– Mexico border (and, in so doing, crossing other intangible borders) in search of a better life. Two examples of border literature, Luis Alberto Urrea's Into the Beautiful North (2009) and Graciela Limón's The River Flows North (2009), have been selected for analysis. These texts, in describing various diaspora spaces—to enlist Avtar Brah's term (Cartographies of Diaspora. London: Routledge, 1996)—also examine how those who do not migrate are affected by migration. In Writing the Goodlife: Mexican American Literature and the Environment (Tucson: University of Arizona Press, 2016), Priscilla Solis Ybarra reveals how the past century and a half's Mexican-American literature contains valuable new approaches to creating and sustaining new forms of transnational relations between humans, and ecologically sound relationships between humans and nature.
- Full Text:
- Date Issued: 2019
Intersecting Diasporas:
- Authors: Naidu, Samantha
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/158034 , vital:40141 , DOI: 10.1080/18125441.2019.1661597
- Description: With increased mobility enabled by evolving technology, the world experiences higher rates of migration and globalisation than ever before. This phenomenon has led, in recent years, to a high volume of literature about migration and diaspora, i.e. literature which deals with the general theme of transnationalism. The term transnational, in its simplest guise, refers to the relations between citizens of different nation states and the networks which link them. It also refers to the complex subjectivity of those who migrate. Scholars emphasise that transnationalism, because of heterogeneity and diversity, gives rise to a site for dynamic social and cultural change. At the same time, continuity is a necessary feature of this site. The co-existence of change and continuity (a focused process of adaptation and assimilation which simultaneously considers the role of memory, the past, and ties to homeland) then is also a defining element of transnationalism.
- Full Text:
- Date Issued: 2019
- Authors: Naidu, Samantha
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/158034 , vital:40141 , DOI: 10.1080/18125441.2019.1661597
- Description: With increased mobility enabled by evolving technology, the world experiences higher rates of migration and globalisation than ever before. This phenomenon has led, in recent years, to a high volume of literature about migration and diaspora, i.e. literature which deals with the general theme of transnationalism. The term transnational, in its simplest guise, refers to the relations between citizens of different nation states and the networks which link them. It also refers to the complex subjectivity of those who migrate. Scholars emphasise that transnationalism, because of heterogeneity and diversity, gives rise to a site for dynamic social and cultural change. At the same time, continuity is a necessary feature of this site. The co-existence of change and continuity (a focused process of adaptation and assimilation which simultaneously considers the role of memory, the past, and ties to homeland) then is also a defining element of transnationalism.
- Full Text:
- Date Issued: 2019
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