Article
Multidisciplinary Sciences
Vincent Chaptal, Veronica Zampieri, Benjamin Wiseman, Cedric Orelle, Juliette Martin, Kim-Anh Nguyen, Alexia Gobet, Margot Di Cesare, Sandrine Magnard, Waqas Javed, Jad Eid, Arnaud Kilburg, Marine Peuchmaur, Julien Marcoux, Luca Monticelli, Martin Hogbom, Guy Schoehn, Jean-Michel Jault, Ahcene Boumendjel, Pierre Falson
Summary: This study resolved three outward-facing conformations of BmrA, a multidrug ABC transporter, using x-ray crystallography and cryo-electron microscopy. It was found that two R6G molecules bind to the drug-binding cavity, inducing a rearrangement of TM1-2 and highlighting local flexibility. Simulations showed that in the absence of R6G, the cavity quickly closed after drug release, while in the presence of R6G, the cavity remained open.
Article
Physiology
Clemens V. Farr, Ali El-Kasaby, Fatma A. Erdem, Sonja Sucic, Michael Freissmuth, Walter Sandtner
Summary: Creatine is an important component of cellular energy metabolism, regulated by the creatine transporter CRT-1. We analyzed the kinetics of CRT-1 and found it utilized the concentration gradient of NaCl and the membrane potential for high concentrative power. Our mathematical model of CRT-1 transport cycle accurately reproduced experimental data and revealed that destabilizing binary complexes is crucial for maintaining cytosolic creatine concentrations.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Chemistry, Organic
Alex H. Y. Chan, Terence C. S. Ho, Daniel R. Parle, Finian J. Leeper
Summary: Suppression of pyruvate dehydrogenase complex (PDHc) is a mechanism for cancer cells to manifest the Warburg effect. However, recent evidence suggests that whether PDHc activity is suppressed or activated depends on the type of cancer. The PDHc E1 subunit (PDH E1) is a thiamine pyrophosphate (TPP)-dependent enzyme, catalysing the first and rate-limiting step of PDHc; thus, there is a need for selective PDH E1 inhibitors.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mu Li, Xintong Zhang, Sixiang Chen, Hanhe Liu, Yuan-Wei Zhang
Summary: This study reveals a novel structural characteristic of the neurotransmitter sodium symporter (NSS) family, specifically in TuriSERT, and demonstrates the unique substrate binding site and 1:1 stoichiometry of sodium-substrate binding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Flora Szeri, Valentina Corradi, Fatemeh Niaziorimi, Sylvia Donnelly, Gwenaelle Conseil, Susan P. C. Cole, D. Peter Tieleman, Koen van de Wetering
Summary: ABCC6 inactivating mutations cause the rare hereditary mineralization disorder pseudoxanthoma elasticum. ABCC6 is proposed to be an ATP-dependent ATP efflux pump, with a potential ATP-binding site in its substrate-binding cavity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Yun Wang, Anthony K. Mittermaier
Summary: ITC is a robust and nearly universal experimental approach for characterizing enzyme kinetics by measuring the heat produced or absorbed during catalysis. The newly developed 2D-ITC method allows for mapping reaction velocity as a function of two substrate concentrations in a single experiment, providing a high level of detail with a large quantity of catalytic rate measurements. In a proof-of-principle application to rabbit muscle pyruvate kinase, the method identified the enzyme's mechanism and revealed a previously unreported allosteric effect of phenylalanine on ATP inhibition.
ANALYTICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Jessica Fernandes Scortecci, Laurie L. Molday, Susan B. Curtis, Fabian A. Garces, Pankaj Panwar, Filip Van Petegem, Robert S. Molday
Summary: ABCA4 is a crucial transporter protein that flips N-retinylidene-phosphatidylethanolamine (N-Ret-PE) in photoreceptor membranes. Mutations in ABCA4 are associated with vision loss. The structural analysis provides insight into the substrate binding and transport mechanism of ABCA4.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Yuchong Yang, Tanya K. Ronson, Dingyu Hou, Jieyu Zheng, Ilma Jahovic, Kai Hong Luo, Jonathan R. Nitschke
Summary: A trigonal prismatic cage containing anthracene-centered ligands was formed through a reaction involving photogenerated singlet oxygen. Heating resulted in the reversion to the initial equilibrium system. Guest binding was observed to influence the formation of specific structures.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Rishav Mitra, Varun V. Gadkari, Ben A. Meinen, Carlo P. M. van Mierlo, Brandon T. Ruotolo, James C. A. Bardwell
Summary: ATP-independent chaperone Spy demonstrates substrate-specific behavior when interacting with the complex client apoflavodoxin, tightly binding to partially unfolded states to convert into a pure holdase.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Yoshihiro Owatari, Shuta Iseki, Daiji Ogata, Junpei Yuasa
Summary: Electron injection triggers sustainable electrocatalytic chain reactions, releasing solvent molecules and forming redox active guest molecules. One-electron reduction produces AQ(-), which is stable and powerful enough to reduce AQH-CH2CN, resulting in the formation of AQ and CH3CN. These mild and sustainable electrocatalytic chain reactions control charge-transfer complex formation, achieving molecular recognition with a catalytic electron-triggered switch.
Review
Chemistry, Medicinal
Kosuke Kawaguchi, Tsuneo Imanaka
Summary: The ATP-binding cassette (ABC) transporters are a large family of membrane proteins found in living organisms. They play important roles in cellular homeostasis by utilizing ATP hydrolysis to transport various substances across membranes. In humans, four ABC transporters belong to the D subfamily and are involved in the transport of acyl-CoAs and vitamin B-12. Mutations in these transporters can cause genetic diseases. This review summarizes the targeting mechanism and physiological functions of ABCD transporters and discusses insights from disease-causing mutations and cryo-electron microscopy studies.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2022)
Review
Biochemistry & Molecular Biology
Cedric Orelle, Lutz Schmitt, Jean-Michel Jault
Summary: Microorganisms rely on ATP-binding cassette (ABC) transporters, which are membrane proteins, to exchange with their environment for nutrients and remove toxic compounds. While these transporters play a protective role in organisms by expelling unrelated compounds, they can also contribute to resistance to therapeutic treatments. Interestingly, some multidrug ABC transporters exhibit high levels of ATPase activity even without substrates. This inherent activity allows them to efficiently transport drugs before they penetrate into the cell.
TRENDS IN MICROBIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yubing Dong, Yi Lin, Wanyu Liu, Wei Zhang, Yinong Jiang, Wei Song
Summary: The study investigated the lipid profile in hypertensive disorders of pregnancy (HDP) patients, finding significantly altered levels of plasma triglycerides, total cholesterol, LDL-C, and HDL-C compared to normotensive controls. ANP was shown to inhibit ABCA1 and ABCG1 expression at both mRNA and protein levels, leading to impaired cholesterol efflux, possibly explaining the decreased HDL-C levels in HDP patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Samiksha Kukal, Debleena Guin, Chitra Rawat, Shivangi Bora, Manish Kumar Mishra, Priya Sharma, Priyanka Rani Paul, Neha Kanojia, Gurpreet Kaur Grewal, Shrikant Kukreti, Luciano Saso, Ritushree Kukreti
Summary: ABCG2 is a widely distributed protein in different cell types that plays a crucial role in maintaining cellular homeostasis and protecting tissues against xenobiotic insults, but its expression is influenced by various pathophysiological conditions. Therapeutic interventions should focus on regulating levels of ABCG2 rather than directly inhibiting its function to avoid serious side effects.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Weiquan Li, Ning Xu, Xiangui Meng, Hongmei Yang, Tiexi Yu, Qi Miao, Hongwei Yang, Bo Hai, Wen Xiao, Xiaoping Zhang
Summary: SLC17A9, a vesicular ATP transport protein, has been identified as a potential diagnostic and prognostic risk biomarker for clear cell renal cell carcinoma (ccRCC). Aberrant expression levels of SLC17A9 were confirmed in both cell lines and clinical tissues. Mechanistically, SLC17A9 could upregulate the expression of PTHLH, promoting epithelial-mesenchymal transition (EMT) in ccRCC. Functionally, SLC17A9 knockdown inhibited the proliferation, migration, and invasion of renal cancer cells, while overexpression led to increased cell viability and a more malignant phenotype in vitro. The overexpression of SLC17A9 in vivo significantly contributed to tumor growth. Additionally, SLC17A9 may be associated with vorinostat drug resistance.
Article
Biophysics
David B. Sauer, Nathan K. Karpowich, Jin Mei Song, Da-Neng Wang
BIOPHYSICAL JOURNAL
(2015)
Article
Biochemistry & Molecular Biology
Nathan K. Karpowich, Jin Mei Song, Nicolette Cocco, Da-Neng Wang
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Kwangsoo Kim, Sharmistha Mitra, Gang Wu, Vladimir Berka, Jinmei Song, Ye Yu, Sebastien Poget, Da-Neng Wang, Ah-Lim Tsai, Ming Zhou
Article
Biochemistry & Molecular Biology
Nathan K. Karpowich, Jinmei Song, Da-Neng Wang
JOURNAL OF MOLECULAR BIOLOGY
(2016)
Review
Biophysics
Da-Neng Wang, Heather Stieglitz, Jennifer Marden, Lukas K. Tamm
BIOPHYSICAL JOURNAL
(2013)
Article
Biochemistry & Molecular Biology
Andrew B. Waight, Bryan K. Czyzewski, Da-Neng Wang
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2013)
Article
Physiology
Christopher Mulligan, Gabriel A. Fitzgerald, Da-Neng Wang, Joseph A. Mindell
JOURNAL OF GENERAL PHYSIOLOGY
(2014)
Article
Multidisciplinary Sciences
Nathan K. Karpowich, Da-Neng Wang
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2013)
Bibliography
Cell Biology
Da-Neng Wang, Lu-Chang Qin
Article
Biochemical Research Methods
David B. Sauer, Da-Neng Wang
Article
Biology
David B. Sauer, Noah Trebesch, Jennifer J. Marden, Nicolette Cocco, Jinmei Song, Akiko Koide, Shohei Koide, Emad Tajkhorshid, Da-Neng Wang
Article
Multidisciplinary Sciences
David B. Sauer, Jinmei Song, Bing Wang, Jacob K. Hilton, Nathan K. Karpowich, Joseph A. Mindell, William J. Rice, Da-Neng Wang
Summary: Citrate plays a crucial role in the energy metabolism and fatty acid synthesis. Cryo-electron microscopy structures reveal the inhibition mechanism of NaCT and the impact of mutations on epilepsy.
Article
Biochemistry & Molecular Biology
David B. Sauer, Bing Wang, Joseph C. Sudar, Jinmei Song, Jennifer Marden, William J. Rice, Da-Neng Wang
Summary: The DASS family consists of various proteins, with NaCT and LaINDY showing high structural similarity to the VcINDY fold and sharing a similar transport mechanism. Studying different structural states helps in understanding their transport cycle.
Article
Multidisciplinary Sciences
David B. Sauer, Jennifer J. Marden, Joseph C. Sudar, Jinmei Song, Christopher Mulligan, Da-Neng Wang
Summary: In this study, the authors demonstrate that the VcINDY protein couples sodium and substrate binding through a cooperative mechanism by conformational selection. The results provide strong evidence for the sodium-dependent formation of the substrate binding site.
NATURE COMMUNICATIONS
(2022)