Search

Your search keyword '"Holloway, Stephen"' showing total 41 results
Start Over Author "Holloway, Stephen" Publication Year Range Last 10 years
41 results on '"Holloway, Stephen"'

2. DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation

Author

Kwon, Youngho, Rösner, Heike, Zhao, Weixing, Selemenakis, Platon, He, Zhuoling, Kawale, Ajinkya S., Katz, Jeffrey N., Rogers, Cody M., Neal, Francisco E., Badamchi Shabestari, Aida, Petrosius, Valdemaras, Singh, Akhilesh K., Joel, Marina Z., Lu, Lucy, Holloway, Stephen P., Burma, Sandeep, Mukherjee, Bipasha, Hromas, Robert, Mazin, Alexander, Wiese, Claudia, Sørensen, Claus S., and Sung, Patrick

Published
2023
Full Text
View/download PDF

6. Insights into the Role of the Unusual Disulfide Bond in Copper-Zinc Superoxide Dismutase*

Author

Sea, Kevin, Sohn, Se Hui, Durazo, Armando, Sheng, Yuewei, Shaw, Bryan F, Cao, Xiaohang, Taylor, Alexander B, Whitson, Lisa J, Holloway, Stephen P, Hart, P John, Cabelli, Diane E, Gralla, Edith Butler, and Valentine, Joan Selverstone

Subjects
Rare Diseases, Neurodegenerative, Genetics, Amyotrophic Lateral Sclerosis, Apoproteins, Calorimetry, Differential Scanning, Disulfides, Electron Spin Resonance Spectroscopy, Humans, Mass Spectrometry, Metals, Mutant Proteins, Mutation, Oxidative Stress, Protein Binding, Protein Conformation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Spectrometry, Mass, Electrospray Ionization, Spectrophotometry, Superoxide Dismutase, Superoxides, Zinc, Amyotrophic Lateral Sclerosis (ALS), Copper, Disulfide, Metalloenzyme, Superoxide Ion, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology
Abstract

The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. We determined x-ray crystal structures of metal-bound and metal-deficient hC57S SOD1. C57S hSOD1 isolated from yeast contained four zinc ions per protein dimer and was structurally very similar to wild type. The addition of copper to this four-zinc protein gave properly reconstituted 2Cu,2Zn C57S hSOD, and its spectroscopic properties indicated that the coordination geometry of the copper was remarkably similar to that of holo wild type hSOD1. In contrast, the addition of copper and zinc ions to apo C57S human SOD1 failed to give proper reconstitution. Using pulse radiolysis, we determined SOD activities of yeast and human SOD1s lacking disulfide bonds and found that they were enzymatically active at ∼10% of the wild type rate. These results are contrary to earlier reports that the intrasubunit disulfide bonds in SOD1 are essential for SOD activity. Kinetic studies revealed further that the yeast mutant SOD1 had less ionic attraction for superoxide, possibly explaining the lower rates. Saccharomyces cerevisiae cells lacking the sod1 gene do not grow aerobically in the absence of lysine, but expression of C57S SOD1 increased growth to 30-50% of the growth of cells expressing wild type SOD1, supporting that C57S SOD1 retained a significant amount of activity.

Published
2015

16. The 1H, 15N and 13C resonance assignments of the low-complexity domain from the oncogenic fusion protein EWS-FLI1.

Author

Johnson, Courtney N., Xu, Xiaoping, Holloway, Stephen P., and Libich, David S.

Abstract

The RNA-binding protein EWS is a multifunctional protein with roles in the regulation of transcription and RNA splicing. It is one of the FET (FUS, EWS and TAF15) family of RNA binding proteins that contain an intrinsically disordered, low-complexity N-terminal domain. The FET family proteins are prone to chromosomal translocations, often fusing their low-complexity domain with a transcription factor derived DNA-binding domain, that are oncogenic drivers in several leukemias and sarcomas. The fusion protein disrupts the normal function of cells through non-canonical DNA binding and alteration of normal transcriptional programs. However, the exact mechanism for how the intrinsically disordered domain contributes to aberrant DNA binding and abnormal transcription is unknown. The purification and 1H, 13C, and 15N backbone resonance assignments of the amino terminal domain comprising 264 residues of EWS is described. This segment is common to all known EWS-fusions that are the hallmark of the pediatric cancer Ewing sarcoma. This domain is intrinsically disordered and features significant sequence degeneracy resulting in spectra with poor chemical shift dispersion. To alleviate this problem, the domain was divided into three overlapping fragments, reducing the complexity of the spectra and enabling almost complete backbone resonance assignment of the full domain. These solution NMR chemical shift assignments represent the first steps towards understanding, at atomic resolution, how the low-complexity domain of EWS contributes to the aberrant functions of its oncogenic fusion proteins. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

17. An iterative process produces oxamniquine derivatives that kill the major species of schistosomes infecting humans

Author

Guzman, Meghan A., primary, Rugel, Anastasia R., additional, Tarpley, Reid S., additional, Alwan, Sevan N., additional, Chevalier, Frédéric D., additional, Kovalskyy, Dmytro P., additional, Cao, Xiaohang, additional, Holloway, Stephen P., additional, Anderson, Timothy J. C., additional, Taylor, Alexander B., additional, McHardy, Stanton F., additional, and LoVerde, Philip T., additional

Published
2020
Full Text
View/download PDF

18. Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

Author

Chevalier, Frederic D., Le Clec'H, Winka, Mcdew-white, Marina, Menon, Vinay, Guzman, Meghan A., Holloway, Stephen P., Cao, Xiaohang, Taylor, Alexander B., Kinung'Hi, Safari, Gouvras, Anouk N., Webster, Bonnie L., Webster, Joanne P., Emery, Aidan M., Rollinson, David, Garba Djirmay, Amadou, Al Mashikhi, Khalid M., Al Yafae, Salem, Idris, Mohamed A., Mone, Helene, Mouahid, Gabriel, Hart, P. John, Loverde, Philip T., Anderson, Timothy J. C., Chevalier, Frederic D., Le Clec'H, Winka, Mcdew-white, Marina, Menon, Vinay, Guzman, Meghan A., Holloway, Stephen P., Cao, Xiaohang, Taylor, Alexander B., Kinung'Hi, Safari, Gouvras, Anouk N., Webster, Bonnie L., Webster, Joanne P., Emery, Aidan M., Rollinson, David, Garba Djirmay, Amadou, Al Mashikhi, Khalid M., Al Yafae, Salem, Idris, Mohamed A., Mone, Helene, Mouahid, Gabriel, Hart, P. John, Loverde, Philip T., and Anderson, Timothy J. C.

Abstract

Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29-14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate

Published
2019
Full Text
View/download PDF

19. Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

Author

Chevalier, Frédéric D, Le Clec’h, Winka, McDew-White, Marina, Menon, Vinay, Guzman, Meghan A, Holloway, Stephen P, Cao, Xiaohang, Taylor, Alexander B, Kinung'hi, Safari, Gouvras, Anouk N, Webster, BL, Webster, Joanne P, Emery, AM, Rollinson, D, Garba Djirmay, Amadou, Al Mashikhi, Khalid M, Al Yafae, Salem, Idris, Mohamed A, Moné, Hélène, Mouahid, Gabriel, Hart, P John, LoVerde, Philip T, Anderson, Timothy JC, Chevalier, Frédéric D, Le Clec’h, Winka, McDew-White, Marina, Menon, Vinay, Guzman, Meghan A, Holloway, Stephen P, Cao, Xiaohang, Taylor, Alexander B, Kinung'hi, Safari, Gouvras, Anouk N, Webster, BL, Webster, Joanne P, Emery, AM, Rollinson, D, Garba Djirmay, Amadou, Al Mashikhi, Khalid M, Al Yafae, Salem, Idris, Mohamed A, Moné, Hélène, Mouahid, Gabriel, Hart, P John, LoVerde, Philip T, and Anderson, Timothy JC

Abstract

Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29-14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate

Published
2019

30. Conclusion

Author

Holloway Stephen

Published
2018

32. Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

Author

Chevalier, Frédéric D., primary, Le Clec’h, Winka, additional, McDew-White, Marina, additional, Menon, Vinay, additional, Guzman, Meghan A., additional, Holloway, Stephen P., additional, Cao, Xiaohang, additional, Taylor, Alexander B., additional, Kinung'hi, Safari, additional, Gouvras, Anouk N., additional, Webster, Bonnie L., additional, Webster, Joanne P., additional, Emery, Aidan M., additional, Rollinson, David, additional, Garba Djirmay, Amadou, additional, Al Mashikhi, Khalid M., additional, Al Yafae, Salem, additional, Idris, Mohamed A., additional, Moné, Hélène, additional, Mouahid, Gabriel, additional, Hart, P. John, additional, LoVerde, Philip T., additional, and Anderson, Timothy J. C., additional

Published
2019
Full Text
View/download PDF

33. Oxamniquine resistance alleles are widespread in Old WorldSchistosoma mansoniand predate drug deployment

Author

Chevalier, Frédéric D., primary, Clec’h, Winka Le, additional, McDew-White, Marina, additional, Menon, Vinay, additional, Guzman, Meghan A., additional, Holloway, Stephen P., additional, Cao, Xiaohang, additional, Taylor, Alexander B., additional, Kinung’hi, Safari, additional, Gouvras, Anouk N., additional, Webster, Bonnie L., additional, Webster, Joanne P., additional, Emery, Aidan M., additional, Rollinson, David, additional, Djirmay, Amadou Garba, additional, Al Mashikhi, Khalid M., additional, Yafae, Salem Al, additional, Idris, Mohamed A., additional, Moné, Hélène, additional, Mouahid, Gabriel, additional, Hart, P. John, additional, LoVerde, Philip T., additional, and Anderson, Timothy JC., additional

Published
2019
Full Text
View/download PDF

34. Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral Infection

Author

Zhang, Shen-Ying, primary, Clark, Nathaniel E., additional, Freije, Catherine A., additional, Pauwels, Elodie, additional, Taggart, Allison J., additional, Okada, Satoshi, additional, Mandel, Hanna, additional, Garcia, Paula, additional, Ciancanelli, Michael J., additional, Biran, Anat, additional, Lafaille, Fabien G., additional, Tsumura, Miyuki, additional, Cobat, Aurélie, additional, Luo, Jingchuan, additional, Volpi, Stefano, additional, Zimmer, Bastian, additional, Sakata, Sonoko, additional, Dinis, Alexandra, additional, Ohara, Osamu, additional, Garcia Reino, Eduardo J., additional, Dobbs, Kerry, additional, Hasek, Mary, additional, Holloway, Stephen P., additional, McCammon, Karen, additional, Hussong, Stacy A., additional, DeRosa, Nicholas, additional, Van Skike, Candice E., additional, Katolik, Adam, additional, Lorenzo, Lazaro, additional, Hyodo, Maki, additional, Faria, Emilia, additional, Halwani, Rabih, additional, Fukuhara, Rie, additional, Smith, Gregory A., additional, Galvan, Veronica, additional, Damha, Masad J., additional, Al-Muhsen, Saleh, additional, Itan, Yuval, additional, Boeke, Jef D., additional, Notarangelo, Luigi D., additional, Studer, Lorenz, additional, Kobayashi, Masao, additional, Diogo, Luisa, additional, Fairbrother, William G., additional, Abel, Laurent, additional, Rosenberg, Brad R., additional, Hart, P. John, additional, Etzioni, Amos, additional, and Casanova, Jean-Laurent, additional

Published
2018
Full Text
View/download PDF

35. Structural and enzymatic insights into species-specific resistance to schistosome parasite drug therapy

Author

Taylor, Alexander B., primary, Roberts, Kenneth M., additional, Cao, Xiaohang, additional, Clark, Nathaniel E., additional, Holloway, Stephen P., additional, Donati, Enrica, additional, Polcaro, Chiara M., additional, Pica-Mattoccia, Livia, additional, Tarpley, Reid S., additional, McHardy, Stanton F., additional, Cioli, Donato, additional, LoVerde, Philip T., additional, Fitzpatrick, Paul F., additional, and Hart, P. John, additional

Published
2017
Full Text
View/download PDF

37. Engineering a Putative Zinc Binding Site in SOD5

Author

Romero, Claudia Moreno, primary, Peterson, Ryan L., additional, Taylor, Alexander B., additional, Holloway, Stephen P., additional, Galaleldeen, Ahmad, additional, Culotta, Valeria Cizewski, additional, and Hart, P. John, additional

Published
2016
Full Text
View/download PDF

38. Structural and Functional Characterization of the Enantiomers of the Antischistosomal Drug Oxamniquine

Author

Taylor, Alexander B., primary, Pica-Mattoccia, Livia, additional, Polcaro, Chiara M., additional, Donati, Enrica, additional, Cao, Xiaohang, additional, Basso, Annalisa, additional, Guidi, Alessandra, additional, Rugel, Anastasia R., additional, Holloway, Stephen P., additional, Anderson, Timothy J. C., additional, Hart, P. John, additional, Cioli, Donato, additional, and LoVerde, Philip T., additional

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results