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913 results on '"Wilson, Derek"'

58. Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection

Author

Mesquita, Rafael D., Vionette-Amaral, Raquel J., Lowenberger, Carl, Rivera-Pomar, Rolando, Monteiro, Fernando A., Minx, Patrick, Spieth, John, Carvalho, A. Bernardo, Panzera, Francisco, Lawson, Daniel, Torres, André Q., Ribeiro, Jose M. C., Sorgine, Marcos H. F., Waterhouse, Robert M., Montague, Michael J., Abad-Franch, Fernando, Alves-Bezerra, Michele, Amaral, Laurence R., Araujo, Helena M., Araujo, Ricardo N., Aravind, L., Atella, Georgia C., Azambuja, Patricia, Berni, Mateus, Bittencourt-Cunha, Paula R., Braz, Gloria R. C., Calderón-Fernández, Gustavo, Carareto, Claudia M. A., Christensen, Mikkel B., Costa, Igor R., Costa, Samara G., Dansa, Marilvia, Daumas-Filho, Carlos R. O., De-Paula, Iron F., Dias, Felipe A., Dimopoulos, George, Emrich, Scott J., Esponda-Behrens, Natalia, Fampa, Patricia, Fernandez-Medina, Rita D., da Fonseca, Rodrigo N., Fontenele, Marcio, Fronick, Catrina, Fulton, Lucinda A., Gandara, Ana Caroline, Garcia, Eloi S., Genta, Fernando A., Giraldo-Calderón, Gloria I., Gomes, Bruno, Gondim, Katia C., Granzotto, Adriana, Guarneri, Alessandra A., Guigó, Roderic, Harry, Myriam, Hughes, Daniel S. T., Jablonka, Willy, Jacquin-Joly, Emmanuelle, Juárez, M. Patricia, Koerich, Leonardo B., Lange, Angela B., Latorre-Estivalis, José Manuel, Lavore, Andrés, Lawrence, Gena G., Lazoski, Cristiano, Lazzari, Claudio R., Lopes, Raphael R., Lorenzo, Marcelo G., Lugon, Magda D., Majerowicz, David, Marcet, Paula L., Mariotti, Marco, Masuda, Hatisaburo, Megy, Karine, Melo, Ana C. A., Missirlis, Fanis, Mota, Theo, Noriega, Fernando G., Nouzova, Marcela, Nunes, Rodrigo D., Oliveira, Raquel L. L., Oliveira-Silveira, Gilbert, Ons, Sheila, Orchard, Ian, Pagola, Lucia, Paiva-Silva, Gabriela O., Pascual, Agustina, Pavan, Marcio G., Pedrini, Nicolás, Peixoto, Alexandre A., Pereira, Marcos H., Pike, Andrew, Polycarpo, Carla, Prosdocimi, Francisco, Ribeiro-Rodrigues, Rodrigo, Robertson, Hugh M., Salerno, Ana Paula, Salmon, Didier, Santesmasses, Didac, Schama, Renata, Seabra-Junior, Eloy S., Silva-Cardoso, Livia, Silva-Neto, Mario A. C., Souza-Gomes, Matheus, Sterkel, Marcos, Taracena, Mabel L., Tojo, Marta, Tu, Zhijian Jake, Tubio, Jose M. C., Ursic-Bedoya, Raul, Venancio, Thiago M., Walter-Nuno, Ana Beatriz, Wilson, Derek, Warren, Wesley C., Wilson, Richard K., Huebner, Erwin, Dotson, Ellen M., and Oliveira, Pedro L.

Published
2015

59. Recruitment of FBXO22 for targeted degradation of NSD2

Author

Nie, David Y., Tabor, John R., Li, Jianping, Kutera, Maria, St-Germain, Jonathan, Hanley, Ronan P., Wolf, Esther, Paulakonis, Ethan, Kenney, Tristan M. G., Duan, Shili, Shrestha, Suman, Owens, Dominic D. G., Maitland, Matthew E. R., Pon, Ailing, Szewczyk, Magdalena, Lamberto, Anthony Joseph, Menes, Michael, Li, Fengling, Penn, Linda Z., Barsyte-Lovejoy, Dalia, Brown, Nicholas G., Barsotti, Anthony M., Stamford, Andrew W., Collins, Jon L., Wilson, Derek J., Raught, Brian, Licht, Jonathan D., James, Lindsey I., and Arrowsmith, Cheryl H.

Abstract

Targeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases to target proteins for proteasomal degradation. Here we describe a TPD strategy involving the recruitment of FBXO22 to induce degradation of the histone methyltransferase and oncogene NSD2. UNC8732 facilitates FBXO22-mediated degradation of NSD2 in acute lymphoblastic leukemia cells harboring the NSD2 gain-of-function mutation p.E1099K, resulting in growth suppression, apoptosis and reversal of drug resistance. The primary amine of UNC8732 is metabolized to an aldehyde species, which engages C326 of FBXO22 to recruit the SCFFBXO22Cullin complex. We further demonstrate that a previously reported alkyl amine-containing degrader targeting XIAP is similarly dependent on SCFFBXO22. Overall, we present a potent NSD2 degrader for the exploration of NSD2 disease phenotypes and a new FBXO22-recruitment strategy for TPD.

Published
2024
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62. The Medical School Learning Environment Survey: An Examination of Its Factor Structure and Relationship to Student Performance and Satisfaction

Author

Rusticus, Shayna, Worthington, Anne, Wilson, Derek, and Joughin, Karen

Abstract

The Medical School Learning Environment Survey (MSLES) was used with a sample of 311 undergraduate medical students in British Columbia, Canada, to assess the seven scales of Medical Breadth of Interest, Personal Breadth of Interest, Emotional Climate, Flexibility, Meaningful Learning Experience, Organization, Nurturance and Student-Student Interaction. Confirmatory factor analysis was used to support the validity of the MSLES when used with this sample.

Published
2014
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70. Racial Socialization's Moderating Effect between Poverty Stress and Psychological Symptoms for African American Youth

Author

Wilson, Derek, Foster, Jennifer, and Anderson, Shawanda

Abstract

Research indicates that African Americans living in an oppressive society may be at an increased risk of experiencing psychological symptoms. Oppressive society has been defined as the continual denial of resources to marginalized groups. This study examined the possible moderating effects of racial socialization (using Scale of Racial Socialization-Adolescent) in the relationship between poverty and psychological symptoms (externalizing and internalizing symptoms). The sample consisted of 105 African American adolescents, aged 11 to 15, from a large midwestern city. Racial socialization was expected to reduce psychological symptomatology. There was an unexpected finding of a positive relationship between racial socialization and externalizing symptoms. Although significant moderating effects were found for racial socialization, no protective effect was demonstrated in this study. Future research directions are discussed. (Contains 4 tables, 2 figures and 2 notes.)

Published
2009
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71. Time-resolved electrospray mass spectrometry--a brief history

Author

Lento, Cristina, Audette, Gerald F., and Wilson, Derek J.

Subjects
Protein folding -- Analysis, Catalysis -- Analysis -- Models, Microfluidics -- Methods -- Analysis, Mass spectrometry -- Methods -- Analysis -- History, Ionization -- Methods -- Properties -- Analysis, Enzymes -- Chemical properties -- Analysis, Hydrogen -- Isotopes, Enzyme kinetics -- Analysis -- Models, Chemistry
Abstract

This review describes the evolution of time-resolved electrospray ionization mass spectrometry (TRESI-MS), a technology that was developed in large part at Western University. TRESI-MS was initially designed to characterize rapid chemical and biochemical reactions occurring on the millisecond time scale without need for a chromophore. Early TRESI-MS setups usually consisted of continuous-flow rapid mixers with a fixed tee for analysis of a single time point, and later adjustable reaction chamber devices allowing for automatic tracking of the reaction over time. Advances in instrumentation design over the years have resulted in improved time resolution, with microfluidic device implementation allowing for coupling to hydrogen-deuterium exchange (HDX) experiments. Areas of application that will be discussed include the investigation of protein folding intermediates, identification of enzyme-substrate intermediates in the pre-steady state, and the use of time- resolved HDX to study the dynamics of weakly structured protein regions. While some limitations still persist with the method, the continued development of TRESI-MS and related approaches paves the way to a promising future and the study of unexplored application areas. Key words: mass spectrometry, electrospray ionization mass spectrometry, time-resolved, kinetics, protein folding, enzyme catalysis, hydrogen-deuterium exchange. La presente etude decrit l'evolution de la spectrometrie de masse a ionisation par electronebulisation resolue en temps (TRESI-MS), une technologie qui fut elaboree en grande partie a la Western University. A l'origine, la TRESI-MS fut concue pour caracteriser les reactions chimiques et biochimiques rapides qui se produisaient a l'echelle de la milliseconde sans presence necessaire d'un chromophore. Les premiers appareils de TRESI-MS consistaient generalement en des melangeurs rapides a flux continu equipes d'un << tee >> fixe permettant d'effectuer des analyses ponctuelles, puis, plus tard, en des dispositifs a chambres de reaction ajustables offrant la possibilite de realiser le suivi automatique des reactions au cours du temps. Des progres realises dans la conception de l'instrumentation au fil des ans ont permis d'ameliorer la resolution temporelle, notamment la mise en place d'appareils de microfluidique qui permirent de realiser des experiences de couplage avec l'echange hydrogene- deuterium (HDX). Nous presenterons, entre autres champs d'application, l'etude des intermediaires du repliement proteique, l'identification des intermediaires du complexe enzyme-substrat dans l'etat de pre-equilibre et l'utilisation de HDX resolu en temps pour l'etude de la dynamique des regions proteiques faiblement structurees. Bien qu'elle montre encore quelques limites, l'amelioration continue de la TRESI-MS et des techniques auxquelles elle est associee ouvre la voie a un avenir prometteur et a l'etude de champs d'application inexplores. [Traduit par la Redaction] Mots-cles : spectrometrie de masse, spectrometrie de masse a ionisation par electronebulisation, resolution en temps, cinetique, repliement proteique, catalyse enzymatique, echange hydrogene-deuterium., Introduction Mass spectrometry (MS) has become one of the most sensitive bioanalytical tools for the structural characterization of (bio)molecules, driven by continual instrumental advancements since its origin stemming from the [...]

Published
2015
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77. Population genomics of Drosophila suzukii reveal longitudinal population structure and signals of migrations in and out of the continental United States

Author

Lewald, Kyle M, primary, Abrieux, Antoine, additional, Wilson, Derek A, additional, Lee, Yoosook, additional, Conner, William R, additional, Andreazza, Felipe, additional, Beers, Elizabeth H, additional, Burrack, Hannah J, additional, Daane, Kent M, additional, Diepenbrock, Lauren, additional, Drummond, Francis A, additional, Fanning, Philip D, additional, Gaffney, Michael T, additional, Hesler, Stephen P, additional, Ioriatti, Claudio, additional, Isaacs, Rufus, additional, Little, Brian A, additional, Loeb, Gregory M, additional, Miller, Betsey, additional, Nava, Dori E, additional, Rendon, Dalila, additional, Sial, Ashfaq A, additional, Bezerra da Silva, Cherre S, additional, Stockton, Dara G, additional, Van Timmeren, Steven, additional, Wallingford, Anna, additional, Walton, Vaughn M, additional, Wang, Xingeng, additional, Zhao, Bo, additional, Zalom, Frank G, additional, and Chiu, Joanna C, additional

Published
2021
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79. Bifunctional ligand design for modulating mutant p53 aggregation in cancer† †Electronic supplementary information (ESI) available: Experimental procedures, synthetic schemes, 1H and 13C NMR characterization, pKa values, speciation diagrams, Zn affinity determination and respective HypSpec data fitting, and NCI-60 in vitro cytotoxicity data for LI and LH (PDF). Crystallographic data for ZnLICl and ZnLHCl (CIF). CCDC 1947980 and 1947981. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c9sc04151f

Author

Miller, Jessica J., Blanchet, Anaïs, Orvain, Christophe, Nouchikian, Lucienne, Reviriot, Yasmin, Clarke, Ryan M., Martelino, Diego, Wilson, Derek, Gaiddon, Christian, and Storr, Tim

Subjects
Chemistry
Abstract

Iodination of a bifunctional ligand framework restores p53 function by interacting with and inhibiting mutant p53 aggregation., Protein misfolding and aggregation contributes to the development of a wide range of diseases. In cancer, over 50% of diagnoses are attributed to p53 malfunction due to missense mutations, many of which result in protein misfolding and accelerated aggregation. p53 mutations also frequently result in alteration or loss of zinc at the DNA-binding site, which increases aggregation via nucleation with zinc-bound p53. Herein, we designed two novel bifunctional ligands, LI and LH, to modulate mutant p53 aggregation and restore zinc binding using a metallochaperone approach. Interestingly, only the incorporation of iodine function in LI resulted in modulation of mutant p53 aggregation, both in recombinant and cellular environments. Native mass spectrometry shows a protein–ligand interaction for LI, as opposed to LH, which is hypothesized to lead to the distinct difference in the p53 aggregation profile for the two ligands. Incorporation of a di-2-picolylamine binding unit into the ligand design provided efficient intracellular zinc uptake, resulting in metallochaperone capability for both LI and LH. The ability of LI to reduce mutant p53 aggregation results in increased restoration of p53 transcriptional function and mediates both caspase-dependent and -independent cell death pathways. We further demonstrate that LI exhibits minimal toxicity in non-cancerous organoids, and that it is well tolerated in mice. These results demonstrate that iodination of our ligand framework restores p53 function by interacting with and inhibiting mutant p53 aggregation and highlights LI as a suitable candidate for comprehensive in vivo anticancer preclinical evaluations.

Published
2019

91. Ensembl Genomes 2013: scaling up access to genome-wide data

Author

Kersey, Paul Julian, Allen, James E., Christensen, Mikkel, Davis, Paul, Falin, Lee J., Grabmueller, Christoph, Hughes, Daniel Seth Toney, Humphrey, Jay, Kerhornou, Arnaud, Khobova, Julia, Langridge, Nicholas, McDowall, Mark D., Maheswari, Uma, Maslen, Gareth, Nuhn, Michael, Ong, Chuang Kee, Paulini, Michael, Pedro, Helder, Toneva, Iliana, Tuli, Mary Ann, Walts, Brandon, Williams, Gareth, Wilson, Derek, Youens-Clark, Ken, Monaco, Marcela K., Stein, Joshua, Wei, Xuehong, Ware, Doreen, Bolser, Daniel M., Howe, Kevin Lee, Kulesha, Eugene, Lawson, Daniel, and Staines, Daniel Michael

Published
2014
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95. Population structure of Drosophila suzukii and signals of multiple invasions into the continental United States

Author

Lewald, Kyle M., primary, Abrieux, Antoine, additional, Wilson, Derek A., additional, Lee, Yoosook, additional, Conner, William R., additional, Andreazza, Felipe, additional, Beers, Elizabeth H., additional, Burrack, Hannah J., additional, Daane, Kent M., additional, Diepenbrock, Lauren, additional, Drummond, Francis A., additional, Fanning, Philip D., additional, Gaffney, Michael T., additional, Hesler, Stephen P., additional, Ioriatti, Claudio, additional, Isaacs, Rufus, additional, Little, Brian A., additional, Loeb, Gregory M., additional, Miller, Betsey, additional, Nava, Dori E., additional, Rendon, Dalila, additional, Sial, Ashfaq A., additional, Silva, Cherre B. da, additional, Stockton, Dara G., additional, Van Timmeren, Steven, additional, Wallingford, Anna, additional, Walton, Vaughn M., additional, Wang, Xingeng, additional, Zhao, Bo, additional, Zalom, Frank G., additional, and Chiu, Joanna C., additional

Published
2021
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98. Evolution of genes and genomes on the Drosophila phylogeny

Author

Clark, Andrew G., Eisen, Michael B., Smith, Douglas R., Bergman, Casey M., Oliver, Brian, Markow, Therese A., Kaufman, Thomas C., Kellis, Manolis, Gelbart, William, Iyer, Venky N., Pollard, Daniel A., Sackton, Timothy B., Larracuente, Amanda M., Singh, Nadia D., Abad, Jose P., Abt, Dawn N., Adryan, Boris, Aguade, Montserrat, Akashi, Hiroshi, Anderson, Wyatt W., Aquadro, Charles F., Ardell, David H., Arguello, Roman, Artieri, Carlo G., Barbash, Daniel A., Barker, Daniel, Barsanti, Paolo, Batterham, Phil, Batzoglou, Serafim, Begun, Dave, Bhutkar, Arjun, Blanco, Enrico, Bosak, Stephanie A., Bradley, Robert K., Brand, Adrianne D., Brent, Michael R., Brooks, Angela N., Brown, Randall H., Butlin, Roger K., Caggese, Corrado, Calvi, Brian R., Bernardo de Carvalho, A., Caspi, Anat, Castrezana, Sergio, Celniker, Susan E., Chang, Jean L., Chapple, Charles, Chatterji, Sourav, Chinwalla, Asif, Civetta, Alberto, Clifton, Sandra W., Comeron, Josep M., Costello, James C., Coyne, Jerry A., Daub, Jennifer, David, Robert G., Delcher, Arthur L., Delehaunty, Kim, Do, Chuong B., Ebling, Heather, Edwards, Kevin, Eickbush, Thomas, Evans, Jay D., Filipski, Alan, Findeiß, Sven, Freyhult, Eva, Fulton, Lucinda, Fulton, Robert, Garcia, Ana C. L., Gardiner, Anastasia, Garfield, David A., Garvin, Barry E., Gibson, Greg, Gilbert, Don, Gnerre, Sante, Godfrey, Jennifer, Good, Robert, Gotea, Valer, Gravely, Brenton, Greenberg, Anthony J., Griffiths-Jones, Sam, Gross, Samuel, Guigo, Roderic, Gustafson, Erik A., Haerty, Wilfried, Hahn, Matthew W., Halligan, Daniel L., Halpern, Aaron L., Halter, Gillian M., Han, Mira V., Heger, Andreas, Hillier, LaDeana, Hinrichs, Angie S., Holmes, Ian, Hoskins, Roger A., Hubisz, Melissa J., Hultmark, Dan, Huntley, Melanie A., Jaffe, David B., Jagadeeshan, Santosh, Jeck, William R., Johnson, Justin, Jones, Corbin D., Jordan, William C., Karpen, Gary H., Kataoka, Eiko, Keightley, Peter D., Kheradpour, Pouya, Kirkness, Ewen F., Koerich, Leonardo B., Kristiansen, Karsten, Kudrna, Dave, Kulathinal, Rob J., Kumar, Sudhir, Kwok, Roberta, Lander, Eric, Langley, Charles H., Lapoint, Richard, Lazzaro, Brian P., Lee, So-Jeong, Levesque, Lisa, Li, Ruiqiang, Lin, Chiao-Feng, Lin, Michael F., Lindblad-Toh, Kerstin, Llopart, Ana, Long, Manyuan, Low, Lloyd, Lozovsky, Elena, Lu, Jian, Luo, Meizhong, Machado, Carlos A., Makalowski, Wojciech, Marzo, Mar, Matsuda, Muneo, Matzkin, Luciano, McAllister, Bryant, McBride, Carolyn S., McKernan, Brendan, McKernan, Kevin, Mendez-Lago, Maria, Minx, Patrick, Mollenhauer, Michael U., Montooth, Kristi, Mount, Stephen M., Mu, Xu, Myers, Eugene, Negre, Barbara, Newfeld, Stuart, Nielsen, Rasmus, Noor, Mohamed A. F., O'Grady, Patrick, Pachter, Lior, Papaceit, Montserrat, Parisi, Matthew J., Parisi, Michael, Parts, Leopold, Pedersen, Jakob S., Pesole, Graziano, Phillippy, Adam M., Ponting, Chris P., Pop, Mihai, Porcelli, Damiano, Powell, Jeffrey R., Prohaska, Sonja, Pruitt, Kim, Puig, Marta, Quesneville, Hadi, Ravi Ram, Kristipati, Rand, David, Rasmussen, Matthew D., Reed, Laura K., Reenan, Robert, Reily, Amy, Remington, Karin A., Rieger, Tania T., Ritchie, Michael G., Robin, Charles, Rogers, Yu-Hui, Rohde, Claudia, Rozas, Julio, Rubenfield, Marc J., Ruiz, Alfredo, Russo, Susan, Salzberg, Steven L., Sanchez-Gracia, Alejandro, Saranga, David J., Sato, Hajime, Schaeffer, Stephen W., Schatz, Michael C., Schlenke, Todd, Schwartz, Russell, Segarra, Carmen, Singh, Rama S., Sirot, Laura, Sirota, Marina, Sisneros, Nicholas B., Smith, Chris D., Smith, Temple F., Spieth, John, Stage, Deborah E., Stark, Alexander, Stephan, Wolfgang, Strausberg, Robert L., Strempel, Sebastian, Sturgill, David, Sutton, Granger, Sutton, Granger G., Tao, Wei, Teichmann, Sarah, Tobari, Yoshiko N., Tomimura, Yoshihiko, Tsolas, Jason M., Valente, Vera L. S., Venter, Eli, Craig Venter, J., Vicario, Saverio, Vieira, Filipe G., Vilella, Albert J., Villasante, Alfredo, Walenz, Brian, Wang, Jun, Wasserman, Marvin, Watts, Thomas, Wilson, Derek, Wilson, Richard K., Wing, Rod A., Wolfner, Mariana F., Wong, Alex, Ka-Shu Wong, Gane, Wu, Chung-I, Wu, Gabriel, Yamamoto, Daisuke, Yang, Hsiao-Pei, Yang, Shiaw-Pyng, Yorke, James A., Yoshida, Kiyohito, Zdobnov, Evgeny, Zhang, Peili, Zhang, Yu, Zimin, Aleksey V., Baldwin, Jennifer, Abdouelleil, Amr, Abdulkadir, Jamal, Abebe, Adal, Abera, Brikti, Abreu, Justin, Christophe Acer, St, Aftuck, Lynne, Alexander, Allen, An, Peter, Anderson, Erica, Anderson, Scott, Arachi, Harindra, Azer, Marc, Bachantsang, Pasang, Barry, Andrew, Bayul, Tashi, Berlin, Aaron, Bessette, Daniel, Bloom, Toby, Blye, Jason, Boguslavskiy, Leonid, Bonnet, Claude, Boukhgalter, Boris, Bourzgui, Imane, Brown, Adam, Cahill, Patrick, Channer, Sheridon, Cheshatsang, Yama, Chuda, Lisa, Citroen, Mieke, Collymore, Alville, Cooke, Patrick, Costello, Maura, D'Aco, Katie, Daza, Riza, De Haan, Georgius, DeGray, Stuart, DeMaso, Christina, Dhargay, Norbu, Dooley, Kimberly, Dooley, Erin, Doricent, Missole, Dorje, Passang, Dorjee, Kunsang, Dupes, Alan, Elong, Richard, Falk, Jill, Farina, Abderrahim, Faro, Susan, Ferguson, Diallo, Fisher, Sheila, Foley, Chelsea D., Franke, Alicia, Friedrich, Dennis, Gadbois, Loryn, Gearin, Gary, Gearin, Christina R., Giannoukos, Georgia, Goode, Tina, Graham, Joseph, Grandbois, Edward, Grewal, Sharleen, Gyaltsen, Kunsang, Hafez, Nabil, Hagos, Birhane, Hall, Jennifer, Henson, Charlotte, Hollinger, Andrew, Honan, Tracey, Huard, Monika D., Hughes, Leanne, Hurhula, Brian, Erii Husby, M, Kamat, Asha, Kanga, Ben, Kashin, Seva, Khazanovich, Dmitry, Kisner, Peter, Lance, Krista, Lara, Marcia, Lee, William, Lennon, Niall, Letendre, Frances, LeVine, Rosie, Lipovsky, Alex, Liu, Xiaohong, Liu, Jinlei, Liu, Shangtao, Lokyitsang, Tashi, Lokyitsang, Yeshi, Lubonja, Rakela, Lui, Annie, MacDonald, Pen, Magnisalis, Vasilia, Maru, Kebede, Matthews, Charles, McCusker, William, McDonough, Susan, Mehta, Teena, Meldrim, James, Meneus, Louis, Mihai, Oana, Mihalev, Atanas, Mihova, Tanya, Mittelman, Rachel, Mlenga, Valentine, Montmayeur, Anna, Mulrain, Leonidas, Navidi, Adam, Naylor, Jerome, Negash, Tamrat, Nguyen, Thu, Nguyen, Nga, Nicol, Robert, Norbu, Choe, Norbu, Nyima, Novod, Nathaniel, O'Neill, Barry, Osman, Sahal, Markiewicz, Eva, Oyono, Otero L., Patti, Christopher, Phunkhang, Pema, Pierre, Fritz, Priest, Margaret, Raghuraman, Sujaa, Rege, Filip, Reyes, Rebecca, Rise, Cecil, Rogov, Peter, Ross, Keenan, Ryan, Elizabeth, Settipalli, Sampath, Shea, Terry, Sherpa, Ngawang, Shi, Lu, Shih, Diana, Sparrow, Todd, Spaulding, Jessica, Stalker, John, Stange-Thomann, Nicole, Stavropoulos, Sharon, Stone, Catherine, Strader, Christopher, Tesfaye, Senait, Thomson, Talene, Thoulutsang, Yama, Thoulutsang, Dawa, Topham, Kerri, Topping, Ira, Tsamla, Tsamla, Vassiliev, Helen, Vo, Andy, Wangchuk, Tsering, Wangdi, Tsering, Weiand, Michael, Wilkinson, Jane, Wilson, Adam, Yadav, Shailendra, Young, Geneva, Yu, Qing, Zembek, Lisa, Zhong, Danni, Zimmer, Andrew, Zwirko, Zac, Alvarez, Pablo, Brockman, Will, Butler, Jonathan, Chin, CheeWhye, Grabherr, Manfred, Kleber, Michael, Mauceli, Evan, and MacCallum, Iain

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Drosophila 12 Genomes Consortium; Project Leaders; Andrew G. Clark (corresponding author) [1]; Michael B. Eisen (corresponding author) [2, 3]; Douglas R. Smith (corresponding author) [4]; Casey M. Bergman (corresponding [...]

Published
2007
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99. Hydrogen/deuterium scrambling during quadrupole time-of-flight MS/MS analysis of a zinc-binding protein domain

Author

Ferguson, Peter L., Pan, Jingxi, Wilson, Derek J., Dempsey, Brian, Lajoie, Gilles, Shilton, Brian, and Konermann, Lars

Subjects
Proteins -- Analysis, Binding proteins -- Research, Hydrogen -- Chemical properties, Hydrogen -- Electric properties, Chemistry
Abstract

It remains an open question as to whether experiments involving collision-induced dissociation (CID) can provide a viable approach for monitoring spatially resolved deuteration levels in electrosprayed polypeptide ions. A number of laboratories reported the successful application of CID following solution-phase H/D exchange (HDX), whereas others found that H/D scrambling precluded site-specific measurements. The aim of the current work is to help clarify the general feasibility of HDX-CID methods, using a 22-residue zinc-bound protein domain (Zn-ZBD) as model system. Metal binding in Zn-ZBD should confer structural rigidity, and the presence of several basic residues should sequester mobile charge carders in the gas phase. Both of these factors were expected to suppress the extent of scrambling. HDX was carded out by employing rapid on-line mixing, thereby mimicking conditions typically encountered in kinetic pulse-labeling studies. Quadrupole time-of-flight MS/MS of pulse-labeled Zn-ZBD provides high sequence coverage. However, the measured fragment deuteration levels do not correlate with the known H-bonding pattern of Zn-ZBD, suggesting the occurrence of extensive scrambling. Instead of showing a uniform distribution, the fragment ions reveal a distinct nonrandom pattern of deuteration levels. In the absence of prior information, these data could erroneously be ascribed to the presence of protected sites. However, the observed patterns clearly originate from other factors; possibly they are caused by modulations of the amide CID efficiency by kinetic isotope effects. It is concluded that scrambling does not represent the only conceptual problem in HDX-CID studies and that control experiments on uniformly labeled samples are essential for ruling out interpretation artifacts.

Published
2007

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