Allosteric modulation of conformational dynamics in human Hsp90α: a computational study
- Penkler, David L, Atilgan, Canan, Tastan Bishop, Özlem
- Authors: Penkler, David L , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/68531 , vital:29276 , http://dx.doi.org/10.1101/198341
- Description: Central to Hsp90’s biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90’s regulatory mechanisms, including its modulation by co-chaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. Here, we utilize homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially-open conformations. Atomistic simulations of these structures demonstrated that bound ATP stabilizes the dimer by ‘tensing’ each protomer, while ADP and apo configurations ‘relax’ the complex by increasing global flexibility. Dynamic residue network analysis revealed regions of the protein involved in intra-protein communication, and identified several overlapping key communication hubs that correlate with known functional sites. Perturbation response scanning analysis identified several potential residue sites capable of modulating conformational change in favour of interstate conversion. For the ATP-bound open conformation, these sites were found to overlap with known Aha1 and client binding sites, demonstrating how naturally occurring forces associated with co-factor binding could allosterically modulate conformational dynamics.
- Full Text:
- Date Issued: 2017
- Authors: Penkler, David L , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/68531 , vital:29276 , http://dx.doi.org/10.1101/198341
- Description: Central to Hsp90’s biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90’s regulatory mechanisms, including its modulation by co-chaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. Here, we utilize homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially-open conformations. Atomistic simulations of these structures demonstrated that bound ATP stabilizes the dimer by ‘tensing’ each protomer, while ADP and apo configurations ‘relax’ the complex by increasing global flexibility. Dynamic residue network analysis revealed regions of the protein involved in intra-protein communication, and identified several overlapping key communication hubs that correlate with known functional sites. Perturbation response scanning analysis identified several potential residue sites capable of modulating conformational change in favour of interstate conversion. For the ATP-bound open conformation, these sites were found to overlap with known Aha1 and client binding sites, demonstrating how naturally occurring forces associated with co-factor binding could allosterically modulate conformational dynamics.
- Full Text:
- Date Issued: 2017
Phototransferred thermoluminescence of α-Al2O3: C: experimental results and empirical models
- Chithambo, Makaiko L, Seneza, Cleophace, Kalita, Jitumani M
- Authors: Chithambo, Makaiko L , Seneza, Cleophace , Kalita, Jitumani M
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/115681 , vital:34215 , https://doi.org/10.1016/j.radmeas.2017.08.009
- Description: The thermoluminescence glow curve of α-Al2O3:C consists of a prominent apparently-single peak and a number of weaker intensity secondary peaks. Phototransferred thermoluminescence (PTTL) from secondary glow peaks in α-Al2O3:C is reported. For completeness and to aid discussion, complementary results for the main peak are included. The problem studied is one of phototransferred thermoluminescence for a system of multiple acceptors and multiple donors. A TL glow curve recorded at 5 °C/s following irradiation to 0.5 Gy shows the main peak (labelled II) at 240 °C and two secondary peaks at 86 °C (peak I) and 360 °C (peak III). Peak I is reproduced under phototransfer after any preheating between 100 and 500 °C. Peak II is also reproduced as a PTTL peak after preheating to any temperature up to 800 °C. For the latter, the duration of preheating matters because if the sample is preheated at 800 °C for say, 6 min, PTTL is obtained but not when this is extended to say, 15 min. No PTTL was observed from peak III at all. A study of the time dependence of the PTTL intensity from peak III, following preheating that removes peaks I and II, shows that its electron trap acts as an acceptor when the duration of illumination to stimulate electrons from deep traps is brief but that when the illumination time is extended, the electron trap for peak III loses some of its trapped electrons to the shallower traps thus acting as a donor trap.
- Full Text: false
- Date Issued: 2017
- Authors: Chithambo, Makaiko L , Seneza, Cleophace , Kalita, Jitumani M
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/115681 , vital:34215 , https://doi.org/10.1016/j.radmeas.2017.08.009
- Description: The thermoluminescence glow curve of α-Al2O3:C consists of a prominent apparently-single peak and a number of weaker intensity secondary peaks. Phototransferred thermoluminescence (PTTL) from secondary glow peaks in α-Al2O3:C is reported. For completeness and to aid discussion, complementary results for the main peak are included. The problem studied is one of phototransferred thermoluminescence for a system of multiple acceptors and multiple donors. A TL glow curve recorded at 5 °C/s following irradiation to 0.5 Gy shows the main peak (labelled II) at 240 °C and two secondary peaks at 86 °C (peak I) and 360 °C (peak III). Peak I is reproduced under phototransfer after any preheating between 100 and 500 °C. Peak II is also reproduced as a PTTL peak after preheating to any temperature up to 800 °C. For the latter, the duration of preheating matters because if the sample is preheated at 800 °C for say, 6 min, PTTL is obtained but not when this is extended to say, 15 min. No PTTL was observed from peak III at all. A study of the time dependence of the PTTL intensity from peak III, following preheating that removes peaks I and II, shows that its electron trap acts as an acceptor when the duration of illumination to stimulate electrons from deep traps is brief but that when the illumination time is extended, the electron trap for peak III loses some of its trapped electrons to the shallower traps thus acting as a donor trap.
- Full Text: false
- Date Issued: 2017
Reconfiguring the OMWESO board game: performing narratives of Buganda material culture
- Authors: Kirumira, Rose Namubiru
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/146512 , vital:38532 , https://www.ru.ac.za/artsofafrica/latestnews/presentationreconfiguringtheomwesoboardgameperformingnarrativesofbug.html
- Description: As a Writer in Residence in the Fine Art Department at Rhodes, she is pursuing research on the omweso board game, which she has reinterpreted in her own sculptural work in recent years. As a sculptor, Dr. Kirumira has produced exhibitions such as “Faces” (1996) and “Personalities” (2010) at Tulifanya Art Gallery in Kampala. Her strength is creating monumental sculptures, and she has produced a number of public monuments and projects such as the sculptures for the Don Bosco Vocational School Chapel, Kamuli, 1997. Working under the renowned Prof. Francis Naggenda, she made the statue of “King Ronald Mutebi” at the Buganda Parliament and the work “Family” at Mulago Hospital Kampala. She also made the two famous sculptures "Mother Uganda" and "UNDP" at the former UNDP Headquarters, and has produced monumental sculptures in Canada, Denmark and China.
- Full Text:
- Date Issued: 2017
- Authors: Kirumira, Rose Namubiru
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/146512 , vital:38532 , https://www.ru.ac.za/artsofafrica/latestnews/presentationreconfiguringtheomwesoboardgameperformingnarrativesofbug.html
- Description: As a Writer in Residence in the Fine Art Department at Rhodes, she is pursuing research on the omweso board game, which she has reinterpreted in her own sculptural work in recent years. As a sculptor, Dr. Kirumira has produced exhibitions such as “Faces” (1996) and “Personalities” (2010) at Tulifanya Art Gallery in Kampala. Her strength is creating monumental sculptures, and she has produced a number of public monuments and projects such as the sculptures for the Don Bosco Vocational School Chapel, Kamuli, 1997. Working under the renowned Prof. Francis Naggenda, she made the statue of “King Ronald Mutebi” at the Buganda Parliament and the work “Family” at Mulago Hospital Kampala. She also made the two famous sculptures "Mother Uganda" and "UNDP" at the former UNDP Headquarters, and has produced monumental sculptures in Canada, Denmark and China.
- Full Text:
- Date Issued: 2017
Roundtable review: cold case: the elusive story of Julie Ward's murder
- Authors: Spencer, Lynda G
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/138894 , vital:37683 , https://doi.org/10.1080/23277408.2017.1362199
- Description: A Death Retold in Truth and Rumour: Kenya, Britain and the Julie Ward Murder by Grace Ahingila Musila is an extraordinary, captivating, thought-provoking and chilling account of the unsolved murder of Julie Ward. Musila points out that this book does not set out to reveal who murdered Julie Ward. Instead, as an academic, she is interested in examining the intertextual process between the rumours around this cold case and the evidence available in various published accounts, such as books, newspapers and court judgements.
- Full Text:
- Date Issued: 2017
- Authors: Spencer, Lynda G
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/138894 , vital:37683 , https://doi.org/10.1080/23277408.2017.1362199
- Description: A Death Retold in Truth and Rumour: Kenya, Britain and the Julie Ward Murder by Grace Ahingila Musila is an extraordinary, captivating, thought-provoking and chilling account of the unsolved murder of Julie Ward. Musila points out that this book does not set out to reveal who murdered Julie Ward. Instead, as an academic, she is interested in examining the intertextual process between the rumours around this cold case and the evidence available in various published accounts, such as books, newspapers and court judgements.
- Full Text:
- Date Issued: 2017
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