Article
Biochemistry & Molecular Biology
Daniel M. Kremer, Costas A. Lyssiotis
Summary: Metabolic reprogramming is common in all cancer types and has become a basis for the success of classic chemotherapy. Contemporary research has led to the development of new small-molecule tools and drugs for studying and targeting tumor metabolism. Allosteric modulation of metabolic enzymes has shown promise in selectively targeting cancer metabolism.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Braelyn M. Page, Tyler A. Martin, Collette L. Wright, Lauren A. Fenton, Maite T. Villar, Qingling Tang, Antonio Artigues, Audrey Lamb, Aron W. Fenton, Liskin Swint-Kruse
Summary: Sequence comparisons of protein homologs can reveal protein properties, but multiple biophysical constraints and noise can weaken the correlation. Testing Zymomonas mobilis PYK revealed functional and structural differences compared to other PYK sequences. Including orphan sequences may obscure the correlation used to predict rheostat positions.
Article
Biochemistry & Molecular Biology
Kathleen M. Meneely, Jeffrey S. McFarlane, Collette L. Wright, Kathryn Vela, Liskin Swint-Kruse, Aron W. Fenton, Audrey L. Lamb
Summary: Human liver pyruvate kinase (hlPYK) catalyzes the formation of pyruvate and ATP from phosphoenolpyruvate (PEP) and ADP. Fructose 1,6-bisphosphate (FBP) serves as an allosteric activator of hlPYK. Zymomonas mobilis pyruvate kinase (ZmPYK) performs a similar function in the Entner-Doudoroff pathway, but does not have FBP as an allosteric activator.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Jingyun Li, Yiliang Yin, Enyuan Zhang, Mang Gui, Ling Chen, Jun Li
Summary: This study found that a skin-derived endogenous peptide, PDHPS1, can inhibit cell proliferation, promote apoptosis, decrease the proportion of cells in S phase, and decrease collagen synthesis in hypertrophic scar fibroblasts. In addition, PDHPS1 treatment was shown to alleviate hypertrophic scarring in a rabbit ear model. The mechanism involves targeting FAK and PKM2, as well as remodeling the metabolic landscape.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Medicinal
Amalyn Nain-Perez, Oscar Nilsson, Aleksei Lulla, Liliana Haversen, Paul Brear, Sara Liljenberg, Marko Hyvonen, Jan Boren, Morten Grotli
Summary: This study describes a novel series of PKL modulators that can allosterically activate or inhibit the enzyme. These modulators were assessed for their effect on PKL activity using liver cell lysates. The study identified compounds that significantly increased PKL activity, as well as compounds that inhibited its activity. Crystal structures provided insights into the conformations of these modulators, which can be used as a reference for designing new modulators.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Nutrition & Dietetics
Umberto Maria Battisti, Chunixa Gao, Fady Akladios, Woonghee Kim, Hong Yang, Cemil Bayram, Ismail Bolat, Metin Kiliclioglu, Nursena Yuksel, Ozlem Ozdemir Tozlu, Cheng Zhang, Jihad Sebhaoui, Shazia Iqbal, Saeed Shoaie, Ahmet Hacimuftuoglu, Serkan Yildirim, Hasan Turkez, Mathias Uhlen, Jan Boren, Adil Mardinoglu, Morten Grotli
Summary: This study presents a new finding that ellagic acid and its derivatives can selectively and potently inhibit liver pyruvate kinase, which may open up new therapeutic options for non-alcoholic fatty liver disease (NAFLD).
Article
Multidisciplinary Sciences
Kevin G. Hicks, Ahmad A. Cluntun, Heidi L. Schubert, Sean R. Hackett, Jordan A. Berg, Paul G. Leonard, Mariana A. Ajalla Aleixo, Youjia Zhou, Alex J. Bott, Sonia R. Salvatore, Fei Chang, Aubrie Blevins, Paige Barta, Samantha Tilley, Aaron Leifer, Andrea Guzman, Ajak Arok, Sarah Fogarty, Jacob M. Winter, Hee-Chul Ahn, Karen N. Allen, Samuel Block, Iara A. Cardoso, Jianping Ding, Ingrid Dreveny, William C. Gasper, Quinn Ho, Atsushi Matsuura, Michael J. Palladino, Sabin Prajapati, Pengkai Sun, Kai Tittmann, Dean R. Tolan, Judith Unterlass, Andrew P. VanDemark, Matthew G. Vander Heiden, Bradley A. Webb, Cai-Hong Yun, Pengkai Zhao, Bei Wang, Francisco J. Schopter, Christopher P. Hill, Maria Cristina Nonato, Florian L. Muller, James E. Cox, Jared Rutter
Summary: Metabolic networks play a crucial role in various cellular processes. Discovering low-affinity protein-metabolite interactions that govern these networks is challenging. A new method, called mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS), was developed to identify such interactions. In a study involving enzymes from human carbohydrate metabolism, 830 protein-metabolite interactions were discovered, including both known and unknown interactions. Some of these interactions were functionally validated, revealing the isoform-specific inhibition of lactate dehydrogenase by long-chain acyl-coenzyme A. The findings suggest that these protein-metabolite interactions contribute to the adaptive metabolic flexibility in different tissues.
Article
Chemistry, Physical
Saleha Anwar, Debarati DasGupta, Alaa Shafie, Fahad A. Alhumaydhi, Suliman A. Alsagaby, Moyad Shahwan, Farah Anjum, Waleed Al Abdulmonem, Sharaf E. Sharaf, Md Imtaiyaz Hassan
Summary: Protein kinase inhibitors are widely used in the treatment of cancer and other diseases. This study focuses on pyruvate dehydrogenase kinase 3 (PDK3) as a potential drug target for cancer therapy. The researchers discovered that tempol is a potent inhibitor of PDK3, and molecular docking and molecular dynamics simulations provided insights into the binding affinity and stability of the PDK3-tempol complex. The study also confirmed the inhibitory action of tempol on PDK3 through binding and inhibition assays.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biochemistry & Molecular Biology
Yonglan Liu, Mingzhen Zhang, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov
Summary: Researchers have used extensive molecular dynamics simulations to decipher the activation and autoinhibition mechanism of c-Abl. The myristoyl group serves as a switch for c-Abl inhibition/activation, and precise SH2/N-lobe interaction is required for full activation. Bcr-Abl allosteric drugs mimic the endogenous myristoyl-mediated autoinhibition state and alter the active-site conformation, affecting the action of ATP-competitive drugs.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Maria A. Voronkova, Heather L. Hansen, Madison P. Cooper, Jacob Miller, Narayanasami Sukumar, Werner J. Geldenhuys, Aaron R. Robart, Bradley A. Webb
Summary: Metabolic reprogramming, including dysregulated glycolytic enzyme PFK1, is a hallmark of cancer. This study reveals that mutations in PFK1 disrupt its activity and alter allosteric regulation, leading to decreased glycolysis in cancer cells but enhanced glycolytic flux under low cellular energy conditions.
BIOCHEMICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Nives Skorja Milic, Klemen Dolinar, Katarina Mis, Urska Matkovic, Marusa Bizjak, Mojca Pavlin, Matej Podbregar, Sergej Pirkmajer
Summary: Inhibition of pyruvate dehydrogenase kinase (PDK) by Dichloroacetate (DCA) can reduce the abundance of PDK isoenzymes in a cell-type-specific manner via both transcriptional and post-transcriptional mechanisms. The differential response of PDK isoenzymes to DCA in cancer cells and muscle cells highlights the importance of understanding the pharmacological effects of DCA in different cell types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Manish Jain, Nirav Dhanesha, Prakash Doddapattar, Manasa K. Nayak, Liang Guo, Anne Cornelissen, Steven R. Lentz, Aloke V. Finn, Anil K. Chauhan
Summary: The glycolytic enzyme PKM2 plays a crucial role in smooth muscle cell phenotype switching and neointimal hyperplasia, with its deletion inhibiting SMC proliferation and migration, reducing neointimal hyperplasia, and modulating various signaling pathways.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nannan Dong, Luna Chen, Shakeel Ahmad, Yicong Cai, Yingqing Duan, Xinwei Li, Yongqiang Liu, Guiai Jiao, Lihong Xie, Shikai Hu, Zhonghua Sheng, Gaoneng Shao, Ling Wang, Shaoqing Tang, Xiangjin Wei, Peisong Hu
Summary: This study identified 10 pyruvate kinase (PK) genes from the rice genome, with OsPK1, OsPK3, OsPK4, OsPK6, and OsPK9 highly expressed in grains. These genes play a crucial role in regulating rice grain quality and yield, and manipulation of certain PK genes through CRISPR/Cas9 system showed potential to improve rice yield and quality. The study highlights the untapped potential of PK gene family in enhancing rice traits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Plant Sciences
Bruno E. Rojas, Matias D. Hartman, Carlos M. Figueroa, Alberto A. Iglesias
Summary: The study analyzed the proteolysis of PEPCK1 in germinating Arabidopsis thaliana seedlings, and found that shorter versions of the protein may be generated by metacaspase-9. Truncated mutants Delta 19 and Delta 101 of AthPEPCK1 exhibited similar kinetic parameters, but activation by malate and inhibition by glucose 6-phosphate were abolished in the .101 mutant. This proteolysis is proposed to adapt the sensitivity to allosteric regulation during the transition from sink to source in germinating seedlings.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Biochemistry & Molecular Biology
Kristyna Bousova, Petr Herman, Jaroslav Vecer, Lucie Bednarova, Lenka Monincova, Pavel Majer, Ladislav Vyklicky, Jiri Vondrasek, Jan Teisinger
Article
Biochemistry & Molecular Biology
Petr Herman, Ales Holoubek, Barbora Brodska
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2019)
Article
Biochemistry & Molecular Biology
Monika Zouharova, Petr Herman, Katerina Hofbauerova, Jiri Vondrasek, Kristyna Bousova
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Optics
V Babin, P. Herman, M. Kucera, M. Nikl, S. Zazubovich
JOURNAL OF LUMINESCENCE
(2019)
Article
Chemistry, Multidisciplinary
Madita Wolter, Domenico Lentini Santo, Petr Herman, Alice Ballone, Federica Centorrino, Tomas Obsil, Christian Ottmann
Article
Biochemistry & Molecular Biology
Kristyna Bousova, Ivan Barvik, Petr Herman, Katerina Hofbauerova, Lenka Monincova, Pavel Majer, Monika Zouharova, Veronika Vetyskova, Klara Postulkova, Jiri Vondrasek
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Monika Zouharova, Jiri Vymetal, Lucie Bednarova, Ondrej Vanek, Petr Herman, Veronika Vetyskova, Klara Postulkova, Petter S. Lingstaadas, Jiri Vondrasek, Kristyna Bousova
Summary: The newly designed CaM/AMBN-Ct fusion protein, consisting of calmodulin and ameloblastin C-terminus, offers potential for expanding Ca2+ detection in biomedicine and biotechnologies. Experimental studies reveal increased stability and preserved function of CaM/AMBN-Ct.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Multidisciplinary Sciences
Marketa Sasinkova, Petr Herman, Ales Holoubek, Dita Strachotova, Petra Otevrelova, Dana Grebenova, Katerina Kuzelova, Barbora Brodska
Summary: Nucleophosmin mutations causing export from the nucleoli to the cytoplasm are common in AML, leading to altered functions. NSC348884 was studied as a potential inhibitor of NPM oligomerization, but was found to not inhibit oligomer formation, with cytotoxicity instead linked to cell adhesion signaling.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Ales Holoubek, Dita Strachotova, Petra Otevrelova, Pavla Roselova, Petr Herman, Barbora Brodska
Summary: The study aims to explore the interaction between NPM and p53, the effect of NPM mutations on p53 in live cells, and the cellular dynamics of NPMmut and p53 after treatment with Selinexor. Results showed that NPM mutations do not affect their interaction with p53, and expression of NPMmut in cells leads to altered p53 regulation and nuclear relocalization post Selinexor treatment, providing new insights for investigating these mutations.
Article
Biology
Matej Horvath, Olivia Petrvalska, Petr Herman, Veronika Obsilova, Tomas Obsil
Summary: The study structurally and biochemically characterized the full-length human DAPK2:14-3-3 complex, investigating the effects of binding to DAPK2 on its dimerization, activation by dephosphorylation of Ser318, and Ca2+/calmodulin binding. The results provide mechanistic insights into 14-3-3-mediated DAPK2 inhibition and highlight the potential of the DAPK2:14-3-3 complex as a target for anti-inflammatory therapies.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biophysics
Rohit Joshi, Pavel Pohl, Dita Strachotova, Petr Herman, Tomas Obsil, Veronika Obsilova
Summary: Nedd4-2, a ubiquitin ligase, is involved in the endocytosis and degradation of target molecules through interactions with 14-3-3 proteins. The binding of 14-3-3 induces structural rearrangement of Nedd4-2, affecting the mobility and emission properties of certain domains. In contrast, the active site of the HECT domain becomes more mobile upon 14-3-3 binding.
BIOPHYSICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Kristyna Bousova, Monika Zouharova, Petr Herman, Veronika Vetyskova, Katerina Jiraskova, Jiri Vondrasek
Summary: TRPM7, a significant protein channel, plays essential roles in cellular functions, Mg2+ homeostasis, and DNA transcription regulation. Recent studies have identified binding regions on its N-termini for intracellular modulators, providing new insights for the development of potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Kristyna Bousova, Monika Zouharova, Petr Herman, Jiri Vymetal, Veronika Vetyskova, Katerina Jiraskova, Jiri Vondrasek
Summary: In this study, we found that the N-terminus of TRPM5 interacts with calcium-binding proteins CaM and S100A1, and these binding regions possess unique basic residues.
Article
Biochemistry & Molecular Biology
Dita Strachotova, Ales Holoubek, Katerina Wolfova, Barbora Brodska, Petr Herman
Summary: Specific C-terminal nucleophosmin (NPM) mutations are associated with acute myeloid leukaemia and cause mislocalization of NPMmut to the cytoplasm. This leads to mislocalization of NPM-interacting partners, including the tumor suppressor p53. We discovered the formation of a ternary complex consisting of NPMmut, p53, and Mdm2, with p53 acting as a bridging link between Mdm2 and NPMmut. Silencing of p53 prevented mislocalization of Mdm2 in the presence of NPMmut.
Article
Chemistry, Analytical
Dita Strachotova, Ales Holoubek, Barbora Brodska, Petr Herman
Summary: This study reports on the two-photon-induced photoconversion of EGFP, which can be permanently converted by intense IR irradiation to a form with a short fluorescence lifetime and spectrally conserved emission. The nonlinear dependence of the photoconversion efficiency on light intensity allows for accurate 3D localization of the converted volume within cellular structures, which is useful for kinetic FLIM applications.
METHODS AND APPLICATIONS IN FLUORESCENCE
(2023)