Article
Biochemistry & Molecular Biology
Antoine Gedeon, Nour Ayoub, Sebastien Brule, Bertrand Raynal, Gouzel Karimova, Muriel Gelin, Ariel Mechaly, Ahmed Haouz, Gilles Labesse, Helene Munier-Lehmann
Summary: Inosine 5' -monophosphate dehydrogenase (IMPDH) is an enzyme that oxidizes inosine 5' monophosphate into xanthosine 5'-monophosphate. It consists of a core domain for catalytic reaction and a less-conserved Bateman domain. Two classes of bacterial IMPDHs have been classified based on their oligomeric and kinetic properties, with MgATP acting as an activator for Class I and a modulator of oligomeric state for Class II. Analysis of deleted variants and chimeras revealed the Bateman domain's role in the different properties of the two classes.
Review
Biochemistry & Molecular Biology
Ruben M. Buey, David Fernandez-Justel, Alberto Jimenez, Jose L. Revuelta
Summary: This article reviews recent developments in understanding the mechanisms of IMPDH regulation, including all layers of allosteric control that fine-tune enzyme activity.
Article
Biochemistry & Molecular Biology
Maria K. Mateyak, Dongming He, Pragati Sharma, Terri Goss Kinzy
Summary: Phosphorylation of eEF1A affects its function, and mutation analysis confirms the importance of several phosphorylation sites, with the S289D mutant's activity being influenced by eEF1B alpha.
Article
Biochemistry & Molecular Biology
Mingxing Wang, Huan Feng, Peng Xu, Qiujin Xie, Jinpeng Gao, Yanzhang Wang, Xiaowei Zhang, Jun Yang, Jeremy D. Murray, Fengli Sun, Chunyan Wang, Ertao Wang, Nan Yu
Summary: The study identified the crucial roles of small GTPases and Nod factor receptor in root hair development and infection process in Medicago truncatula, regulating polar growth and deformation of root hairs through activation and interaction mechanisms.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Amanda J. J. Laseke, Trevor J. J. Boram, Nicholas O. O. Schneider, Jeremy R. R. Lohman, Martin St Maurice
Summary: This study further characterizes the allosteric regulation of Staphylococcus aureus pyruvatecarboxylase (SaPC), revealing the critical role of Arg(21), Lys(46), and Glu(418) residues in the biotin carboxylasedimer interface in the allosteric activation and inhibition of SaPC. The structure of R21A SaPC in complex with acetyl-CoA provides new insights into the acetyl-CoA binding site and its regulatory function.
Article
Biochemistry & Molecular Biology
Minh Huynh, Derek Parsonage, Tom E. Forshaw, Venkat R. Chirasani, G. Aaron Hobbs, Hanzhi Wu, Jingyun Lee, Cristina M. Furdui, Leslie B. Poole, Sharon L. Campbell
Summary: The recent development of mutant-selective inhibitors for the oncogenic KRAS(G12C) allele has generated excitement. These inhibitors covalently engage the mutant C12 thiol, locking the KRAS(G12C) protein in an inactive state. However, there are still mechanistic questions regarding the reactivity of this thiol.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Morihiro Shimizu, Xinya Mi, Futoshi Toyoda, Akiko Kojima, Wei-Guang Ding, Yutaka Fukushima, Mariko Omatsu-Kanbe, Hirotoshi Kitagawa, Hiroshi Matsuura
Summary: Propofol acts as an allosteric modulator of cAMP-dependent gating in HCN channels, affecting the amplitude and voltage dependence of the channel opening.
Review
Biochemistry & Molecular Biology
Daniel Friedrich, Assen Marintchev, Haribabu Arthanari
Summary: In this review, the authors examine the versatility and functionality of HEAT domains in the regulation of mRNA translation initiation. They describe the basic structural architecture of HEAT domains and their involvement in various cellular processes. The focus is on proteins in the translation initiation system that feature HEAT domains, highlighting their remarkably flexible interactions and the functional importance of these domains.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Rossitza N. Irobalieva, Ioannis Manolaridis, Scott M. Jackson, Dongchun Ni, Els Pardon, Henning Stahlberg, Jan Steyaert, Kaspar P. Locher
Summary: This study explores the potential of inhibitors targeting sites other than the substrate binding pocket of ABCG2 and develops novel nanobodies as inhibitors. The results show that these nanobodies allosterically bind to different regions of the nucleotide binding domains and prevent the transporter from undergoing conformational changes required for substrate transport.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Justyna M. Meissner, Katarina Akhmetova, Tomasz Szul, Ekaterina G. Viktorova, Bingdong Sha, Jay M. Bhatt, Eunjoo J. Lee, Richard A. Kahn, George A. Belov, Igor Chesnokov, Elizabeth Sztul
Summary: In this study, we identified the essential role of the HDS3 domain in GBF1 membrane association in mammalian cells and its critical function during Drosophila melanogaster development. We characterized the interdomain arrangements of GBF1 by electron microscopy and proposed models for GBF1 engagement on the membrane.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Victoria R. Mingione, YiTing Paung, Ian R. Outhwaite, Markus A. Seeliger
Summary: The human genome contains over 500 different protein kinases that have tightly regulated activity as signaling enzymes. The enzymatic activity of the conserved kinase domain is influenced by various regulatory inputs, including the binding of regulatory domains, substrates, and post-translational modifications such as autophosphorylation. This review focuses on the allosteric regulation of protein kinases and highlights recent advances in this field.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Oncology
Camille Faure, Rym Djerbi-Bouillie, Anais Domingot, Haniaa Bouzinba-Segard, Said Taouji, Yanis Saidi, Sandra Bernard, Floriane Carallis, Romy Rothe-Walther, Jean-Luc Lenormand, Eric Chevet, Sandrine Bourdoulous
Summary: Therapies targeting the tyrosine kinase receptor HER2 have significantly improved survival of patients with HER2(+) cancer. However, resistance remains a challenge, particularly in the brain metastatic setting. This study identifies a novel class of allosteric HER2 inhibitors, including a compound mimicking Moesin, which effectively inhibits HER2(+) breast tumor progression and shows significant activity on HER2(+) brain tumor progression.
Article
Biochemistry & Molecular Biology
Julie K. L. Sinclair, Wesley E. Robertson, Deepto Mozumdar, Kim Quach, Alanna Schepartz
Summary: In this study, a family of hydrocarbon-stapled peptides, including E1(S), was found to interact with EGFR and inhibit its activity by disrupting JM coiled coil formation. These findings suggest a potential strategy for designing novel allosteric EGFR inhibitors based on mimicking and inhibiting JM interactions.
Article
Entomology
Ruijuan Wang, Zhe Lin, Lizhen Zhou, Caihua Chen, Xianhao Yu, Junjie Zhang, Zhen Zou, Zhiqiang Lu
Summary: In this study, a venom protein called MmRho1 was identified in the endoparasitoid wasp Microplitis mediator. It was found that MmRho1 plays dual roles in the development of the wasp and the suppression of the host insect's cellular immune responses. The protein regulates the levels of vitellogenin and juvenile hormone in the host insect, affecting the wasp's egg production and cocoon formation. MmRho1 enters the host insect's hemocytes and suppresses cellular immune responses.
Article
Allergy
Neelam Panchal, Benjamin Christopher Houghton, Elina Vassalou, Adrian J. Thrasher, Claire Booth
Summary: This study demonstrates that the use of SHP2 inhibitors can restore T-cell function in XLP patients and mouse models lacking SAP. The inhibitors improve immunoglobulin and cytokine secretion, offering a potential novel treatment approach for XLP patients.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Review
Hematology
Wendy Stam, Gabriela Elis Wachholz, Jose Maria de Pereda, Rick Kapur, Ellen van der Schoot, Coert Margadant
Summary: FNAIT is a pregnancy-associated condition caused by maternal alloantibodies against paternally-inherited platelet antigens, most frequently HPA-1a on integrin beta 3. The clinical effects range from no symptoms to fatal intracranial hemorrhage, but underlying pathophysiological determinants are poorly understood.
Article
Cell Biology
Antonio Rodriguez-Blazquez, Arturo Carabias, Alba Moran-Vaquero, Sergio de Cima, Juan R. Luque-Ortega, Carlos Alfonso, Peter Schuck, Jose Antonio Manso, Sandra Macedo-Ribeiro, Carmen Guerrero, Jose M. de Pereda
Summary: C3G activation is regulated by phosphorylation and interaction with Crk adaptor proteins, revealing a two-factor mechanism for tight control of its activity.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Yaokang Wu, Yang Li, Ke Jin, Linpei Zhang, Jianghua Li, Yanfeng Liu, Guocheng Du, Xueqin Lv, Jian Chen, Rodrigo Ledesma-Amaro, Long Liu
Summary: In this study, a 'design-build-test-learn' framework was used to achieve efficient multiplexed optimization of metabolic pathways in Bacillus subtilis. By constructing a platform strain with biosensor signal-amplifying circuits and genetic regulation circuits, and integrating a synthetic CRISPR RNA array blend (ScrABBLE) device, 5,184 combinatorial assemblies targeting three genes were generated. The best GlcN6P producer was screened and engineered for the synthesis of valuable pharmaceuticals, with a N-acetylglucosamine titer of 183.9 g liter(-1) achieved in a 15-liter bioreactor. The potential generic application of the ScrABBLE device was also verified using three fluorescent proteins as a case study.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Young-Kyoung Park, Rodrigo Ledesma-Amaro
Summary: Yarrowia lipolytica is a promising candidate for industrial bioproduction of chemicals, fuels, foods, and pharmaceuticals, thanks to its natural and engineered traits. In recent years, extensive research has been conducted to assess its potential, improve its features, and scale up its processes. The increasing number of publications and patents related to Y. lipolytica demonstrates its importance and potential in the field. Despite the remaining challenges, it is expected that Y. lipolytica will become one of the preferred choices for industrial applications in the near future.
TRENDS IN BIOTECHNOLOGY
(2023)
Correction
Multidisciplinary Sciences
William M. Shaw, Lucie Studena, Kyler Roy, Piotr Hapeta, Nicholas S. McCarty, Alicia E. Graham, Tom Ellis, Rodrigo Ledesma-Amaro
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Jaroslav Hambalko, Peter Gajdos, Jean-Marc Nicaud, Rodrigo Ledesma-Amaro, Michal Tupec, Iva Pichova, Milan Certik
Summary: Research has found that sex pheromone mixtures of certain insect species can produce unique C16 long conjugated fatty acids with two or three conjugated double bonds. The supplementation of fatty acid methyl esters into the medium resulted in the identification of 20 new fatty acids with two or three double bonds. The study proves that Y. lipolytica is capable of synthesizing C16-conjugated fatty acids, and further optimization could lead to increased production of novel fatty acid derivatives with biotechnologically interesting properties.
Article
Biochemical Research Methods
Xiuxia Liu, Manman Sun, Alex Xiong Gao, Rodrigo Ledesma-Amaro, Qiuwu Fang, Yankun Yang, Zhonghu Bai
Summary: In this study, a bicistronic expression cassette based on a leaderless promoter was developed in Corynebacterium glutamicum, which improved the orthogonality and regulatory range of gene expression. The importance of the fore-cistron and SD motif in maintaining the strength of leaderless bicistronic designs was also explored.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Oncology
Sonia Hermoso-Duran, Maria Jose Domper-Arnal, Pilar Roncales, Sonia Vega, Oscar Sanchez-Gracia, Jorge L. L. Ojeda, Angel Lanas, Adrian Velazquez-Campoy, Olga Abian
Summary: The aim of this study was to investigate the interference of colonoscopy bowel preparation on the results of thermal liquid biopsy (TLB). The results showed that bowel preparation altered serum protein levels, affected TLB parameters, and may compromise the diagnostic capability of other liquid-biopsy-based methods. Therefore, blood extraction after bowel preparation for colonoscopy should be avoided.
Article
Chemistry, Medicinal
Maria Nuria Peralta-Moreno, Vanessa Anton-Munoz, David Ortega-Alarcon, Ana Jimenez-Alesanco, Sonia Vega, Olga Abian, Adrian Velazquez-Campoy, Timothy M. Thomson, Jose Manuel Granadino-Roldan, Claudia Machicado, Jaime Rubio-Martinez
Summary: Since the outbreak of the COVID-19 pandemic, there have been over 750 million reported cases of COVID-19 caused by SARS-CoV-2. In order to find effective treatments, intensive research has been conducted on therapeutic agents derived from pharmaceutical repositioning or natural products. This study focuses on identifying inhibitors for the SARS-CoV-2 M-pro main protease dimer using virtual screening of natural compounds derived from Peruvian flora. The compound Hyperoside displayed inhibitory activity against M-pro in vitro, with a K-i value lower than 20 μM, possibly through allosteric modulation.
Article
Microbiology
Jose A. Manso, Arturo Carabias, Zsuzsa Sarkany, Jose M. de Pereda, Pedro Jose Barbosa Pereira, Sandra Macedo-Ribeiro
Summary: The ability of Candida albicans to switch between yeast and hyphal forms is important for its pathogenicity, with CaRas1 playing a key role in this process. This study provides insights into the structure and activation of CaRas1, and identifies a synthetic peptide that can specifically inhibit its activation. These findings open up new possibilities for combating Candida albicans infections.
Article
Multidisciplinary Sciences
Ting Zhang, Qingdong Zeng, Fan Ji, Honghong Wu, Rodrigo Ledesma-Amaro, Qingshan Wei, Hao Yang, Xuhan Xia, Yao Ren, Keqing Mu, Qiang He, Zhensheng Kang, Ruijie Deng
Summary: An in-field molecular diagnostic tool for crop diseases is developed, which utilizes a cheap colorimetric paper and a smartphone for rapid, low-cost, and multiplexed detection of pathogens. The tool can guide the precise application of pesticides, resulting in reduced pesticide usage and improved crop yield.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Tim Habenicht, Katrin Weidenbach, Adrian Velazquez-Campoy, Ruben M. Buey, Monica Balsera, Ruth A. Schmitz
Summary: In the past decade, scientists have focused on small open reading frames (sORFs) that code for proteins less than 70 amino acids in length. These sORFs and corresponding small proteins have been found in all three domains of life, but most of them are still not fully understood. This study reveals the critical role of a small protein called sP36, consisting of only 61 amino acids, in regulating nitrogen metabolism in Methanosarcina mazei. The absence of sP36 significantly delays the growth of M. mazei when transitioning from nitrogen limitation to nitrogen sufficiency. Through in vivo experiments, it is observed that sP36 is dispersed throughout the cytoplasm during nitrogen limitation, but relocates to the cytoplasmic membrane upon shifting the cells to nitrogen sufficiency. In addition, in vitro biochemical analysis shows that sP36 interacts with high affinity with the ammonium transporter AmtB1 and the PII-like protein GlnK1 during nitrogen limitation. Moreover, the interaction between GlnK1 and AmtB1 due to nitrogen upshifts requires the presence of sP36.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biology
Tigran V. Yuzbashev, Evgeniya Y. Yuzbasheva, Olga E. Melkina, Davina Patel, Dmitrii Bubnov, Heiko Dietz, Rodrigo Ledesma-Amaro
Summary: CRISPR/Cas9 technology is revolutionizing microbial cell engineering by enabling marker-free chromosomal integration of DNA. In this study, improvements were made to current Cas9 toolkits to make CRISPR technologies more accessible and easy to implement. These improvements include the ability to switch between marker-free and marker-based integration constructs, redirect multigene integration cassettes to alternative genomic loci, and assemble guide RNA sequences rapidly in vivo. These methodologies were combined with well-established technologies to create a comprehensive toolkit for efficient metabolic engineering using CRISPR/Cas9. The YaliCraft toolkit for Yarrowia lipolytica was developed as a proof of concept, demonstrating the successful integration of markerless DNA and easy assembly of new gRNAs, resulting in the production of homogentisic acid.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Xueqin Lv, Shixiu Cui, Jie Chen, Lingrui Wang, Yanfeng Liu, Jianghua Li, Guocheng Du, Xiaohao Liu, Jian Chen, Rodrigo Ledesma-Amaro, Long Liu
Summary: Food proteins are crucial nutrients in our diet, but their acquisition from the agroindustry leads to environmental pollution and high resource consumption. In this study, a chemo-biocascade catalysis (CBCC) system was developed to convert CO2 into lacto-proteins. The results demonstrate the potential of tandem chemocatalysis and biocatalysis for sustainable protein manufacturing.
Article
Biochemical Research Methods
Alicia Climent-Catala, Ivan Casas-Rodrigo, Suhasini Iyer, Rodrigo Ledesma-Amaro, Thomas E. Ouldridge
Summary: This study investigates the performance of RNA light-up aptamers as transcriptional fluorescent reporters and compares them to protein-based reporters. The researchers found that RNA light-up aptamers exhibit suitable characteristics as transcriptional reporters over time and at the single-cell level, with higher variability in a population compared to protein-based reporters. Additionally, these RNA aptamers may offer faster dynamics compared to fluorescent proteins in E. coli. The implementation of these transcriptional reporters can facilitate transcription-based studies and expand the use of RNA-based circuits in bacterial cells.
ACS SYNTHETIC BIOLOGY
(2023)