Article
Biochemistry & Molecular Biology
Qingshan Luo, Huigang Shi, Xueqing Xu
Summary: Lipopolysaccharide (LPS) is a crucial component of the outer membrane in most Gram-negative bacteria, and its transport from the inner membrane to the outer membrane is facilitated by seven lipopolysaccharide transport proteins. This study presents the cryo-EM structures of LptB(2)FG and LptB(2)FGC from Klebsiella pneumoniae, highlighting the detailed interactions between LPS and the transporter.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(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
Medicine, Research & Experimental
Zhuo-Xun Wu, Qiuyan Mai, Yuqi Yang, Jing-Quan Wang, Hansu Ma, Leli Zeng, Zhe-Sheng Chen, Yihang Pan
Summary: Overexpression of ABCG2 transporter leads to resistance of cancer cells to GSK1070916, and combination with an ABCG2 inhibitor can restore the sensitivity of GSK1070916.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Oncology
Silpa Narayanan, Ying-Fang Fan, Nehaben A. Gujarati, Qiu-Xu Teng, Jing-Quan Wang, Chao-Yun Cai, Yuqi Yang, Anirudh J. Chintalapati, Yixiong Lei, Vijaya L. Korlipara, Zhe-Sheng Chen
Summary: VKNG-1 selectively inhibits ABCG2 transporter and reverses resistance to standard anticancer drugs, providing a potential treatment for ABCG2-mediated MDR in colon cancer.
Article
Multidisciplinary Sciences
Andrzej Harris, Manuel Wagner, Dijun Du, Stefanie Raschka, Lea-Marie Nentwig, Holger Gohlke, Sander H. J. Smits, Ben F. Luisi, Lutz Schmitt
Summary: Pdr5, a member of the ABC transporter superfamily, plays a crucial role in drug efflux through an ATP-driven conformational cycle. The structural analysis reveals that while half of the transporter remains unchanged throughout the cycle, its partner undergoes changes to support a peristaltic motion for pumping molecules.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Laszlo Homolya
Summary: Mutations and polymorphisms in the human ABCG2 transporter can lead to reduced function, potentially causing hyperuricemia and toxic reactions. The genetic alterations in ABCG2 can affect the body's defense mechanisms and the absorption, distribution, and excretion of toxic substances.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Ryuichi Hirota, Zen-ichiro Katsuura, Naoki Momokawa, Hiroki Murakami, Satoru Watanabe, Takenori Ishida, Takeshi Ikeda, Hisakage Funabashi, Akio Kuroda
Summary: In this study, it was found that under specific conditions, a phosphite-dependent strain of Escherichia coli can generate escape mutants. The mutation occurs at position 210 of the transmembrane domain protein HtxC of the phosphorus compound transporter HtxBCDE. The replacement of a specific amino acid residue at this position can reduce the rate of escape mutant generation.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jingxi Liang, Xiuna Yang, Tianyu Hu, Yan Gao, Qi Yang, Haitao Yang, Wei Peng, Xiaoting Zhou, Luke W. Guddat, Bing Zhang, Zihe Rao, Fengjiang Liu
Summary: This study used single particle cryo-electron microscopy (cryo-EM) to determine the structure of the trehalose-specific transporter in Mycobacterium tuberculosis and demonstrated the potential of this technique in exploring dynamic structures of transporters. It provides insights into the trehalose recycling mechanism in Mycobacterium tuberculosis.
Article
Biochemistry & Molecular Biology
Yaolei Mi, Xue Cao, Xuewen Zhu, Weiqiang Chen, Xiangxiao Meng, Huihua Wan, Wei Sun, Sifan Wang, Shilin Chen
Summary: This study identified and characterized 113 ABC transporters in C. sativa, and proposed seven core transporters that may participate in cannabinoid transport. These candidate genes showed high correlation with cannabinoid biosynthetic pathway genes and content, and were highly expressed in cannabinoid biosynthesis and accumulation sites.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Applied
Alba M. Garcia-Lino, Alex Gomez-Gomez, Dafne Garcia-Mateos, Alvaro de la Fuente, Ana I. Alvarez, Oscar J. Pozo, Gracia Merino
Summary: ABCG2 is involved in the secretion of several compounds in milk, with higher levels of tryptophan-related compounds in wild-type mice compared to Abcg2(-/-) mice. The milk-to-plasma ratio of these compounds was also higher in dairy cows carrying the ABCG2 Y581S polymorphism compared to noncarrier animals. In vitro transport assays confirmed these findings and validated differences in the bovine protein variants.
Article
Biochemistry & Molecular Biology
Silpa Narayanan, Zhuo-Xun Wu, Jing-Quan Wang, Hansu Ma, Nikita Acharekar, Jagadish Koya, Sabesan Yoganathan, Shuo Fang, Zhe-Sheng Chen, Yihang Pan
Summary: In this study, GS-9973 showed efficacy in overcoming ABCG2-mediated multidrug resistance in non-small cell lung cancer cells. The drug reversed drug resistance by blocking ABCG2 efflux activity and downregulating ABCG2 expression at the protein level, suggesting it as a potential strategy to overcome MDR in cancers.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Chemistry, Medicinal
Chung-Pu Wu, Megumi Murakami, Yen-Ching Li, Yang-Hui Huang, Yu-Tzu Chang, Tai-Ho Hung, Yu-Shan Wu, Suresh V. Ambudkar
Summary: Imperatorin has the potential to reverse multidrug resistance in ABCG2-overexpressing cancer cells, making it a promising candidate for enhancing the effectiveness of therapeutic agents in tumors with high levels of ABCG2.
Article
Chemistry, Medicinal
Biebele Abel, Megumi Murakami, Dilip K. K. Tosh, Jinha Yu, Sabrina Lusvarghi, Ryan G. G. Campbell, Zhan-Guo Gao, Kenneth A. A. Jacobson, Suresh V. Ambudkar
Summary: Various adenosine receptor nucleoside-like ligands were found to modulate ATP hydrolysis by the multidrug transporter ABCG2. Structure-activity analysis showed a separation of adenosine receptor and ABCG2 activities. Among them, adenine 37c and (N)-meth-anocarba 7-deaza-5'-ethyl ester 60 were potent stimulators of ABCG2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Robert Eckenstaler, Ralf A. Benndorf
Summary: Urate homeostasis in humans is a complex and highly heritable process that involves metabolic urate biosynthesis, renal urate reabsorption, and renal and extrarenal urate excretion. ABCG2 plays a crucial role in urate transport and is associated with early-onset gout.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Gangyang Wang, Lingling Cao, Yafei Jiang, Tao Zhang, Hongsheng Wang, Zhuoying Wang, Jing Xu, Min Mao, Yingqi Hua, Zhengdong Cai, Xiaojun Ma, Shuo Hu, Chenghao Zhou
Summary: This study demonstrates that anlotinib can reverse multidrug resistance in osteosarcoma cells by inhibiting the efflux function of P-glycoprotein 1 (PGP1) and increasing the intracellular accumulation of chemotherapeutic agents. Anlotinib also stimulates the ATPase activity of PGP1. In animal studies, anlotinib combined with doxorubicin shows a significant decrease in tumor growth rate and tumor size.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Anatomy & Morphology
David Smith, Tobias Starborg
Article
Nanoscience & Nanotechnology
Christo N. Nanev, Emmanuel Saridakis, Lata Govada, Sean C. Kassen, Hodaya V. Solomon, Naomi E. Chayen
ACS APPLIED MATERIALS & INTERFACES
(2019)
Article
Chemistry, Multidisciplinary
Mark A. Levenstein, Clara Anduix-Canto, Yi-Yeoun Kim, Mark A. Holden, Carlos Gonzalez Nino, David C. Green, Stephanie E. Foster, Alexander N. Kulak, Lata Govada, Naomi E. Chayen, Sarah Day, Chiu C. Tang, Britta Weinhausen, Manfred Burghammer, Nikil Kapur, Fiona C. Meldrum
ADVANCED FUNCTIONAL MATERIALS
(2019)
Review
Crystallography
Lata Govada, Naomi E. Chayen
Article
Crystallography
Yanmin Li, Lata Govada, Hodaya V. Solomon, Richard B. Gillis, Gary G. Adams, Naomi E. Chayen
Article
Multidisciplinary Sciences
James D. B. O'Sullivan, Sheena M. Cruickshank, Tobias Starborg, Philip J. Withers, Kathryn J. Else
SCIENTIFIC REPORTS
(2020)
Article
Urology & Nephrology
Ester De Leo, Mohamed A. Elmonem, Sante Princiero Berlingerio, Marine Berquez, Beatrice Paola Festa, Roberto Raso, Francesco Bellomo, Tobias Starborg, Manoe Jacoba Janssen, Zeinab Abbaszadeh, Sara Cairoli, Bianca Maria Goffredo, Rosalinde Masereeuw, Olivier Devuyst, Martin Lowe, Elena Levtchenko, Alessandro Luciani, Francesco Emma, Laura Rita Rega
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2020)
Article
Multidisciplinary Sciences
Richard B. Gillis, Hodaya Solomon, Lata Govada, Neil J. Oldham, Vlad Dinu, Shahwar Imran Jiwani, Philemon Gyasi-Antwi, Frank Coffey, Andy Meal, Paul S. Morgan, Stephen E. Harding, John R. Helliwell, Naomi E. Chayen, Gary G. Adams
Summary: The study into the rapid-acting insulin analogue glulisine using a combination of X-ray crystallography and biophysical characterisation provided insights into its structure and function, potentially leading to a better understanding of its pharmacokinetic and pharmacodynamic behavior.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Christo Nanev, Lata Govada, Naomi E. Chayen
Summary: This study explains the nucleation ability of pores by balancing the cohesive energy maintaining the integrity of a crystalline cluster with the destructive energy tending to tear it up. It also demonstrates the importance of having 2D crystals nucleating in the pores first in order to obtain 3D crystals. By filling the pore orifice, the stability of 2D crystal nuclei is increased, as their peripheries are protected from the destructive action of water molecules.
Article
Cardiac & Cardiovascular Systems
Kim A. Dora, Lyudmyla Borysova, Xi Ye, Chloe Powell, Timea Z. Beleznai, Christopher P. Stanley, Vito D. Bruno, Tobias Starborg, Errin Johnson, Anna Pielach, Michael Taggart, Nicola Smart, Raimondo Ascione
Summary: This study investigated the myogenic reactivity of coronary microvascular smooth muscle cells in patients with heart valve disease and identified a correlation between poor myogenic tone and expression of cellular markers.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Sunil Jit R. J. Logantha, Xue J. Cai, Joseph Yanni, Caroline B. Jones, Robert S. Stephenson, Luke Stuart, Gillian Quigley, Oliver Monfredi, Shu Nakao, Il-Young Oh, Tobias Starborg, Ashraf Kitmitto, Akbar Vohra, Robert C. Hutcheon, Antonio F. Corno, Jonathan C. Jarvis, Halina Dobrzynski, Mark R. Boyett, George Hart
Summary: Severe heart failure causes significant effects on Purkinje fibers, including dysfunction, impaired ventricular repolarization, and electrical remodeling, which may increase the risk of fatal arrhythmias in patients.
CIRCULATION-HEART FAILURE
(2021)
Article
Chemistry, Multidisciplinary
Lata Govada, Emmanuel Saridakis, Sean C. Kassen, Ahmad Bin-Ramzi, Rhodri Marc Morgan, Benjamin Chain, John R. Helliwell, Naomi E. Chayen
Summary: CCR5 is a major co-receptor molecule used by HIV-1 to enter cells. X-ray crystallographic studies of the anti-CCR5 antibody RoAb13 together with two peptides suggested a potential blocking effect on HIV entry. This may be useful in the design of a new biomimetic to stimulate an antibody response to CCR5 and block HIV infection.
Article
Biochemistry & Molecular Biology
Francesca Oltrabella, Anthony Jackson-Crawford, Guanhua Yan, Sarah Rixham, Tobias Starborg, Martin Lowe
Summary: This study reveals that the 27 kDa protein Ipip27A is essential for endocytic trafficking of megalin in the proximal renal tubule of zebrafish larvae and functions together with OCRL in supporting proximal tubule endocytosis. Knockout of Ipip27A leads to endocytic phenotype similar to the loss of OCRL, with reduced uptake of fluid-phase and protein cargo, decreased megalin abundance, and altered endosome morphology. These findings identify Ipip27A as a new player in endocytic traffic in the proximal tubule and suggest that defective endocytosis may underlie renal tubulopathy in Lowe syndrome and Dent-2 disease.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biology
Joseph Morgan, Rebecca Yarwood, Tobias Starborg, Guanhua Yan, Martin Lowe
Summary: In this study, the functional requirement for the F-BAR protein pacsin2 in endocytosis in the renal proximal tubule of zebrafish larvae was identified. Pacsin2 is enriched at the apical pole of renal tubular epithelial cells and is necessary for efficient endocytosis and maintenance of megalin uptake and recycling.
Article
Biochemistry & Molecular Biology
Christo N. Nanev, Emmanuel Saridakis, Lata Govada, Naomi E. Chayen
Summary: Growing protein crystals using porous materials can improve diffraction quality, and crystals continue to grow outside the pores after nucleation inside them.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)