Review
Biochemistry & Molecular Biology
Ruby Dhar, Sunil Singh, Indrani Mukherjee, Karthikeyan Pethusamy, Kakali Purkayastha, Prasenjit Das, Jai Bhagwan Sharma, Radhey Shyam Sharma, Subhradip Karmakar
Summary: Implantation in humans involves apposition, adhesion, and invasion of the developing blastocyst into the receptive maternal endometrium. Research has identified key factors in this process, but gaps in our understanding remain. Early pregnancy complications often occur during implantation, when the endometrium is most receptive to the blastocyst.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2021)
Article
Biochemistry & Molecular Biology
Dylan Valleau, Saima M. Sidik, Luiz C. Godoy, Yamilex Acevedo-Sanchez, Charisse Flerida A. Pasaje, My-Hang Huynh, Vern B. Carruthers, Jacquin C. Niles, Sebastian Lourido
Summary: The microneme protein CLAMP, along with the invasion-associated SPATR and a previously uncharacterized protein CLAMP-linked invasion protein (CLIP), forms a complex that is essential for rhoptry discharge following host-cell contact. Phylogenetic analysis suggests that the essential complex components are present across apicomplexans.
Article
Biochemistry & Molecular Biology
Jian Yang, Luis A. R. Carvalho, Shanping Ji, Suyuan Chen, Rui Moreira, Steven H. L. Verhelst
Summary: In this study, 4-oxo-beta-lactams are identified as a novel scaffold for inhibition of rhomboid proteases, and they may serve as both inhibitors and activity-based probes for rhomboid proteases.
Article
Parasitology
Romina Gallenti, Tomas Poklepovich, Monica Florin-Christensen, Leonhard Schnittger
Summary: This study classified and analyzed rhomboid proteins encoded in the genomes of different piroplasmid species, identifying 44 incorrectly classified or misannotated rhomboids. The distinguishing feature of Babesia s.s. from other piroplasmid lineages is the increased number of ROM4 paralogs. Piroplasmid ROM6 is the only rhomboid that is ubiquitous in other organisms.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Article
Parasitology
Xinchao Liu, Chunjing Li, Xiaoyu Li, Muhammad Ehsan, Mingmin Lu, Ke Li, Lixin Xu, Ruofeng Yan, Xiaokai Song, XiangRui Li
Summary: The study revealed the significant role of eIF-5A in T. gondii transmission and pathogenicity by regulating tachyzoite growth, protein synthesis, invasion process, and parasite replication. These findings provide new insights for the development of targeted drugs for controlling T. gondii infection.
PARASITES & VECTORS
(2021)
Review
Microbiology
Jinjin Zhu, Yang Wang, Yuanyuan Cao, Jilong Shen, Li Yu
Summary: Research on Toxoplasma gondii microneme proteins (MICs) has shown their important role in host cell attachment, invasion, motility, and pathogenesis. Specifically focusing on the TgMIC1/4/6 complex can help improve understanding of T. gondii infection and provide a basis for effective control strategies.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Rania Najm, Margarida T. Grilo Ruivo, Diana Marcela Penarete-Vargas, Maguy Hamie, Thomas Mouveaux, Mathieu Gissot, Martin J. Boulanger, Hiba El Hajj, Maryse Lebrun
Summary: Toxoplasmosis is a neglected parasitic disease that requires public health control. The invasion process of Toxoplasma in host cells differs between acute and chronic infection stages, with bradyzoites relying on different proteins for host cell invasion compared to tachyzoites. Vaccination with AMA-RON complexes provides effective protection against acute and chronic toxoplasmosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
David J. Dubois, Sylia Chehade, Marq Jean-Baptiste, Kannan Venugopal, Bohumil Maco, Albert Tell I. Puig, Dominique Soldati-Favre, Sabrina Marion
Summary: This study identifies TgHOOK and TgFTS as endosomal trafficking regulators involved in the apical exocytosis of micronemes. They form a complex with TgHIP and regulate organelle positioning and secretion, impacting processes such as egress, motility, and host cell invasion.
Article
Veterinary Sciences
Yan Yan Song, Qi Qi Lu, Lu Lu Han, Shu Wei Yan, Xin Zhuo Zhang, Ruo Dan Liu, Shao Rong Long, Jing Cui, Zhong Quan Wang
Summary: This study found that serine proteases and cysteine proteases in the ESPs of T. spiralis IIL play main roles in hydrolysing occludin, claudin-1 and E-cad, and upregulating claudin-2 expression. The challenge infection results showed that treatment with specific inhibitors or inhibitor mixtures significantly reduced expulsion of IIL from the gut, and led to reductions in intestinal adult worms compared to the control group. These findings suggest that serine proteases and cysteine proteases may be key target molecules for vaccines against larval invasion and development.
VETERINARY RESEARCH
(2022)
Article
Microbiology
Shu Ye, Matteo Lunghi, Dominique Soldati-Favre
Summary: This study identifies a novel component, SLF, of a guanylate cyclase complex in Toxoplasma gondii that is essential for both acute infection and natural oral infection through the dissemination and persistence of tissue cysts.
Article
Biology
Amit Kumar, Oscar Vadas, Nicolas Dos Santos Pacheco, Xu Zhang, Kin Chao, Nicolas Darvill, Helena O. Rasmussen, Yingqi Xu, Gloria Meng-Hsuan Lin, Fisentzos A. Stylianou, Jan Skov Pedersen, Sarah L. Rouse, Marc L. Morgan, Dominique Soldati-Favre, Stephen Matthews
Summary: The intracellular parasites belonging to the phylum of Apicomplexa employ substrate-dependent gliding motility to invade host cells. The glideosome-associated connector (GAC), a conserved protein, plays a crucial role in this process. The crystal structure of Toxoplasma gondii GAC reveals a unique armadillo repeat region that adopts a closed ring conformation. The properties of GAC suggest that it can adopt multiple conformations from closed to open and extended, and a multi-conformational model is proposed for its assembly and regulation within the glideosome.
Article
Biochemistry & Molecular Biology
Xiaolan Zhang, Yue Wang, Hui Zhu, Zhaohua Zhong
Summary: This study focuses on the role of an esterase (Sse) secreted by Streptococcus pyogenes in pathogenesis. By generating a gene knockout strain and conducting transcriptome analysis, the study reveals that Sse plays a crucial role in GAS virulence and metabolic pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Alessia Possenti, Manlio Di Cristina, Chiara Nicastro, Matteo Lunghi, Valeria Messina, Federica Piro, Lorenzo Tramontana, Simona Cherchi, Mario Falchi, Lucia Bertuccini, Furio Spano
Summary: This study identifies and characterizes two thrombospondin-related proteins, RDF1 and RDF2, in Toxoplasma gondii, showing their key roles in controlling rhoptry discharge, and uncovers a compensatory mechanism contributing to phenotypic plasticity in T. gondii.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Polymer Science
Shayan S. Nazari, Andrew D. Doyle, Kenneth M. Yamada
Summary: Through a 3D in vitro model, it was found that human cancer cells primarily use proteolysis and actin polymerization to breach the basement membrane and expand perforations, with relatively small contribution from myosin II contractility.
Article
Crystallography
Amit Kumar, Xu Zhang, Oscar Vadas, Fisentzos A. Stylianou, Nicolas Dos Santos Pacheco, Sarah L. Rouse, Marc L. Morgan, Dominique Soldati-Favre, Steve Matthews
Summary: A model for parasitic motility has been proposed, suggesting that parasite actin is connected to surface adhesins through a glideosome-associated connector protein (GAC). GAC is responsible for transmitting force to surface adhesins, rather than generating force. Proper connection between actin and adhesins is crucial for motility and invasion.
Article
Chemistry, Medicinal
Ganesha Rai, Kyle R. Brimacombe, Bryan T. Mott, Daniel J. Urban, Xin Hu, Shyh-Ming Yang, Tobie D. Lee, Dorian M. Cheff, Jennifer Kouznetsova, Gloria A. Benavides, Katie Pohida, Eric J. Kuenstner, Diane K. Luci, Christine M. Lukacs, Douglas R. Davies, David M. Dranow, Hu Zhu, Gary Sulikowski, William J. Moore, Gordon M. Stott, Andrew J. Flint, Matthew D. Hall, Victor M. Darley-Usmar, Leonard M. Neckers, Chi V. Dang, Alex G. Waterson, Anton Simeonov, Ajit Jadhav, David J. Maloney
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Jason M. Rohde, Kyle R. Brimacombe, Li Liu, Michael E. Pacold, Adam Yasgar, Dorian M. Cheff, Tobie D. Lee, Ganesha Rai, Bolormaa Baljinnyam, Zhuyin Li, Anton Simeonov, Matthew D. Hall, Min Shen, David M. Sabatini, Matthew B. Boxer
BIOORGANIC & MEDICINAL CHEMISTRY
(2018)
Article
Oncology
Matthew D. Hall, Katherine A. Telma, Ki-Eun Chang, Tobie D. Lee, James P. Madigan, John R. Lloyd, Ian S. Goldlust, James D. Hoeschele, Michael M. Gottesman
Article
Microbiology
Bang Shen, Kevin M. Brown, Tobie D. Lee, L. David Sibley
Article
Multidisciplinary Sciences
Daniel J. Urban, Natalia J. Martinez, Mindy I. Davis, Kyle R. Brimacombe, Dorian M. Cheff, Tobie D. Lee, Mark J. Henderson, Steven A. Titus, Rajan Pragani, Jason M. Rohde, Li Liu, Yuhong Fang, Surendra Karavadhi, Pranav Shah, Olivia W. Lee, Amy Wang, Andrew McIver, Hongchao Zheng, Xiaodong Wang, Xin Xu, Ajit Jadhav, Anton Simeonov, Min Shen, Matthew B. Boxer, Matthew D. Hall
SCIENTIFIC REPORTS
(2017)
Article
Chemistry, Multidisciplinary
Sara E. Kearney, Gergely Zahoranszky-Kohalmi, Kyle R. Brimacombe, Mark J. Henderson, Caitlin Lynch, Tongan Zhao, Kanny K. Wan, Zina Itkin, Christopher Dillon, Min Shen, Dorian M. Cheff, Tobie D. Lee, Danielle Bougie, Ken Cheng, Nathan P. Coussens, Dorjbal Dorjsuren, Richard T. Eastman, Ruili Huang, Michael J. Iannotti, Surendra Karavadhi, Carleen Klumpp-Thomas, Jacob S. Roth, Srilatha Sakamuru, Wei Sun, Steven A. Titus, Adam Yasgar, Ya-Qin Zhang, Jinghua Zhao, Rodrigo B. Andrade, M. Kevin Brown, Noah Z. Burns, Jin K. Cha, Emily E. Mevers, Jon Clardy, Jason A. Clement, Peter A. Crooks, Gregory D. Cuny, Jake Ganor, Jesus Moreno, Lucas A. Morrill, Elias Picazo, Robert B. Susick, Neil K. Garg, Brian C. Goess, Robert B. Grossman, Chambers C. Hughes, Jeffrey N. Johnston, Madeleine M. Joullie, A. Douglas Kinghorn, David G. I. Kingston, Michael J. Krische, Ohyun Kwon, Thomas J. Maimone, Susruta Majumdar, Katherine N. Maloney, Enas Mohamed, Brian T. Murphy, Pavel Nagorny, David E. Olson, Larry E. Overman, Lauren E. Brown, John K. Snyder, John A. Porco, Fatima Rivas, Samir A. Ross, Richmond Sarpong, Indrajeet Sharma, Jared T. Shaw, Zhengren Xu, Ben Shen, Wei Shi, Corey R. J. Stephenson, Alyssa L. Verano, Derek S. Tan, Yi Tang, Richard E. Taylor, Regan J. Thomson, David A. Vosburg, Jimmy Wu, William M. Wuest, Armen Zakarian, Yufeng Zhang, Tianjing Ren, Zhong Zuo, James Inglese, Sam Michael, Anton Simeonov, Wei Zheng, Paul Shinn, Ajit Jadhav, Matthew B. Boxer, Matthew D. Hall, Menghang Xia, Rajarshi Guha, Jason M. Rohde
ACS CENTRAL SCIENCE
(2018)
Article
Pharmacology & Pharmacy
Tobie D. Lee, Olivia W. Lee, Kyle R. Brimacombe, Lu Chen, Rajarshi Guha, Sabrina Lusvarghi, Bethilehem G. Tebase, Carleen Klumpp-Thomas, Robert W. Robey, Suresh V. Ambudkar, Min Shen, Michael M. Gottesman, Matthew D. Hall
MOLECULAR PHARMACOLOGY
(2019)
Article
Biochemical Research Methods
Olivia W. Lee, Shelley Austin, Madison Gamma, Dorian M. Cheff, Tobie D. Lee, Kelli M. Wilson, Joseph Johnson, Jameson Travers, John C. Braisted, Rajarshi Guha, Carleen Klumpp-Thomas, Min Shen, Matthew D. Hall
Article
Cell Biology
Nobu Oshima, Ryo Ishida, Shun Kishimoto, Kristin Beebe, Jeffrey R. Brender, Kazutoshi Yamamoto, Daniel Urban, Ganesha Rai, Michelle S. Johnson, Gloria Benavides, Giuseppe L. Squadrito, Dan Crooks, Joseph Jackson, Abhinav Joshi, Bryan T. Mott, Jonathan H. Shrimp, Michael A. Moses, Min-Jung Lee, Akira Yuno, Tobie D. Lee, Xin Hu, Tamara Anderson, Donna Kusewitt, Helen H. Hathaway, Ajit Jadhav, Didier Picard, Jane B. Trepel, James B. Mitchell, Gordon M. Stott, William Moore, Anton Simeonov, Larry A. Sklar, Jeffrey P. Norenberg, W. Marston Linehan, David J. Maloney, Chi V. Dang, Alex G. Waterson, Matthew Hall, Victor M. Darley-Usmar, Murali C. Krishna, Leonard M. Neckers
Article
Biochemical Research Methods
Jacob S. Roth, Tobie D. Lee, Dorian M. Cheff, Maya L. Gosztyla, Rosita R. Asawa, Carina Danchik, Sam Michael, Anton Simeonov, Carleen Klumpp-Thomas, Kelli M. Wilson, Matthew D. Hall
Article
Chemistry, Medicinal
Ganesha Rai, Daniel J. Urban, Bryan T. Mott, Xin Hu, Shyh-Ming Yang, Gloria A. Benavides, Michelle S. Johnson, Giuseppe L. Squadrito, Kyle R. Brimacombe, Tobie D. Lee, Dorian M. Cheff, Hu Zhu, Mark J. Henderson, Katherine Pohida, Gary A. Sulikowski, David M. Dranow, Md Kabir, Pranav Shah, Elias Padilha, Dingyin Tao, Yuhong Fang, Plamen P. Christov, Kwangho Kim, Somnath Jana, Pavan Muttil, Tamara Anderson, Nitesh K. Kunda, Helen J. Hathaway, Donna F. Kusewitt, Nobu Oshima, Murali Cherukuri, Douglas R. Davies, Jeffrey P. Norenberg, Larry A. Sklar, William J. Moore, Chi Dang, Gordon M. Stott, Leonard Neckers, Andrew J. Flint, Victor M. Darley-Usmar, Anton Simeonov, Alex G. Waterson, Ajit Jadhav, Matthew D. Hall, David J. Maloney
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Jason M. Rohde, Surendra Karavadhi, Rajan Pragani, Li Liu, Yuhong Fang, Weihe Zhang, Andrew McIver, Hongchao Zheng, Qingyang Liu, Mindy Davis, Daniel J. Urban, Tobie D. Lee, Dorian M. Cheff, Melinda Hollingshead, Mark J. Henderson, Natalia J. Martinez, Kyle R. Brimacombe, Adam Yasgar, Wei Zhao, Carleen Klumpp-Thomas, Sam Michael, Joseph Covey, William J. Moore, Gordon M. Stott, Zhuyin Li, Anton Simeonov, Ajit Jadhav, Stephen Frye, Matthew D. Hall, Min Shen, Xiaodong Wang, Samarjit Patnaik, Matthew B. Boxer
Summary: The research focused on neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) and led to the discovery of a series of potent mIDH1 inhibitors, including the atropisomer (+)-119, which showed higher tumoral concentrations and lower 2-HG concentrations in an engineered mouse model compared to the approved drug AG-120.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Plamen P. Christov, Kwangho Kim, Somnath Jana, Ian M. Romaine, Ganesha Rai, Bryan T. Mott, Alexander A. Allweil, Alexander Lamers, Kyle R. Brimacombe, Daniel J. Urban, Tobie D. Lee, Xin Hu, Christine M. Lukacs, Douglas R. Davies, Ajit Jadhav, Matthew D. Hall, Neal Green, William J. Moore, Gordon M. Stott, Andrew J. Flint, David J. Maloney, Gary A. Sulikowski, Alex G. Waterson
Summary: Researchers have developed a series of LDH inhibitors that potentially inhibit the metabolic processes in cancer cells. These new compounds potently inhibit both LDHA and LDHB enzymes, leading to the inhibition of lactate production in cancer cell lines.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Scott J. Eron, Hongwei Huang, Roman Agafonov, Mark E. Fitzgerald, Joe Patel, Ryan E. Michael, Tobie D. Lee, Ashley A. Hart, Jodi Shaulsky, Christopher G. Nasveschuk, Andrew J. Phillips, Stewart L. Fisher, Andrew Good
Summary: The field of targeted protein degradation has rapidly expanded over the past decade, focusing on developing therapies that utilize the ubiquitin-proteasome system to mark proteins for destruction. One common approach involves using heterobifunctional molecules, or degraders, to recruit target proteins to the E3 ligase machinery, forming an indispensable ternary complex. Through the use of hydrogen-deuterium exchange mass spectrometry (HDX-MS), researchers have been able to identify degrader-induced protein-protein interfaces and construct three-dimensional models of these ternary complexes. The study highlights the potential of HDX-MS in providing valuable structural insights into degrader-induced protein-protein interactions in solution, suggesting that the design of future degraders may benefit from methods that accommodate conformational flexibility and non-evolved complementarity at interfaces.
ACS CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Robert W. Robey, Andrea N. Robinson, Fatima Ali-Rahmani, Lyn M. Huff, Sabrina Lusvarghi, Shahrooz Vahedi, Jordan M. Hotz, Andrew C. Warner, Donna Butcher, Jennifer Matta, Elijah F. Edmondson, Tobie D. Lee, Jacob S. Roth, Olivia W. Lee, Min Shen, Kandice Tanner, Matthew D. Hall, Suresh Ambudkar, Michael M. Gottesman
Summary: This research investigated two genes, abcb4 and abcb5, similar to ABCB1 in the zebrafish BBB, unveiling differences in substrate resistance between Abcb4 and Abcb5. Abcb4 demonstrated overlapping substrate specificity with P-gp, suggesting its functional resemblance to P-gp, making zebrafish a potential model for studying P-gp at the BBB.
SCIENTIFIC REPORTS
(2021)