Article
Biology
Amandeep S. Arora, Hsiang-Ling Huang, Ramanpreet Singh, Yoshie Narui, Andrejus Suchenko, Tomoyuki Hatano, Sarah M. Heissler, Mohan K. Balasubramanian, Krishna Chinthalapudi, Pekka Lappalainen
Summary: The structures of actin isoforms have been determined at high resolution, revealing their specific conformations and isoform-specific interfaces. These findings provide important insights into the function of actin isoforms and contribute to our overall understanding of cytoskeletal physiology.
Article
Biochemistry & Molecular Biology
Marco Rabuffetti, Pietro Cannazza, Martina Letizia Contente, Andrea Pinto, Diego Romano, Pilar Hoyos, Andres R. Alcantara, Ivano Eberini, Tommaso Laurenzi, Louise Gourlay, Flavio Di Pisa, Francesco Molinari
Summary: Through structural analysis and computational studies, the research revealed the excellent activity and stereoselectivity of KRED1-Pglu in monoreduction, providing new feasibility for its application as a biocatalyst. After identifying the interaction elements between KRED1-Pglu and bulky diketones, a proposed reaction mechanism and substrate reactivity predictions were made.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jiheon Kim, Wonjae Ko, Ji Mun Yoo, Vinod K. Paidi, Ho Yeon Jang, Michael Shepit, Jongmin Lee, Hogeun Chang, Hyeon Seok Lee, Jinwoung Jo, Byung Hyo Kim, Sung-Pyo Cho, Johan Lierop, Dokyoon Kim, Kug-Seung Lee, Seoin Back, Yung-Eun Sung, Taeghwan Hyeon
Summary: Multi-metal oxide (MMO) materials have potential in catalyst design. However, understanding the (electro)catalytic activity of MMOs is limited due to their complex multi-element nature. This study synthesized uniform-sized multi-metal spinel oxide nanoparticles and systematically studied the contributions of each element to enhance the electrocatalytic oxygen reduction reaction (ORR) activity.
ADVANCED MATERIALS
(2022)
Article
Multidisciplinary Sciences
Izumi Ishigami, Raymond G. Sierra, Zhen Su, Ariana Peck, Cong Wang, Frederic Poitevin, Stella Lisova, Brandon Hayes, Frank R. Moss, Sebastien Boutet, Robert E. Sublett, Chun Hong Yoon, Syun-Ru Yeh, Denis L. Rousseau
Summary: Cytochrome c oxidase (CcO) is a crucial enzyme in cellular respiration, and plays important roles in the oxidative and reductive phases. The research findings indicate that the active site of the O state in CcO, similar to the O-H state, is coordinated by a hydroxide ion and a water molecule. However, a key difference lies in the protonated form of the critical amino acid Y244, which distinguishes O from O-H. These structural characteristics provide valuable insights into the proton translocation mechanism of CcO.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Raju Sen, Srashti Bhardwaj, Krishnendu Bar, Shalu Deshwal, Janakiram Vaitla
Summary: Sulfoxonium ylides are important precursors in organic synthesis, particularly in the synthesis of bioactive compounds and pharmaceuticals. Vinyl sulfoxonium ylides, containing electron-deficient alkene at the ylidic carbon, can generate vinyl carbenes in the presence of metals, allowing for various organic transformations. These compounds can also undergo electrophilic addition reactions with electrophiles at the alpha-position. They are stable and convenient to handle, making them potential replacements for less stable vinyl diazo compounds. This article provides a comprehensive overview of the synthesis and applications of vinyl sulfoxonium ylides, with a focus on metal-mediated and metal-free conditions.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Frederik V. Schmidt, Luca Schulz, Jan Zarzycki, Simone Prinz, Niels N. Oehlmann, Tobias J. Erb, Johannes G. Rebelein
Summary: Nitrogenases are enzymes that can catalyze the reduction of dinitrogen to ammonia. Recent research has shown that nitrogenases can also reduce carbon dioxide and carbon monoxide to hydrocarbon compounds. In this study, the structure of the iron nitrogenase complex from Rhodobacter capsulatus was determined using cryogenic electron microscopy, revealing the presence of an [Fe8S9C-(R)-homocitrate] cluster in the active site. The study also highlighted differences in the interface between the two catalytic halves of the iron and molybdenum nitrogenases, which may influence the nitrogenase mechanism.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Wentong Jiang, Sanduo Zheng
Summary: This study reports the cryoelectron microscopy structures of the GALR1-G(o) and GALR2-G(q) complexes bound to the endogenous ligand galanin or spexin, revealing the structural determinants of GALRs and highlighting the potential role of zinc ion as a modulator of GALR1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Sreekanth Rajan, Ho Sup Yoon
Summary: Malaria, a prevalent infectious disease, poses a serious challenge due to drug-resistant strains. Adopting a chemo-genomics approach can uncover novel targets and mechanisms of action for better drug targeting. Immunosuppressive drugs have been found to inhibit the growth of the malarial parasite, with peptidyl prolyl cis/trans isomerases (PPIases) as the specific targets. This review summarizes the structural insights on Plasmodium PPIases, their inhibitor complexes, and perspectives on drug discovery.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Lvqin Zheng, Zhenggao Zheng, Xiying Li, Guopeng Wang, Kun Zhang, Peijun Wei, Jindong Zhao, Ning Gao
Summary: The major light-harvesting systems for photosynthesis in cyanobacteria and red algae are phycobilisomes (PBS). Cryo-EM structures of two cyanobacterial PBS from Anabaena 7120 and Synechococcus 7002 reveal characteristics of their energy transfer pathways and the critical aromatic residues involved in excitation energy transfer (EET). The structures also suggest active participation of linker proteins in the process of EET within both rods and cores, providing insights into chromophore organization and EET mechanisms in cyanobacterial PBS.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Azadeh Shahsavar, Peter Stohler, Gleb Bourenkov, Iwan Zimmermann, Martin Siegrist, Wolfgang Guba, Emmanuel Pinard, Steffen Sinning, Markus A. Seeger, Thomas R. Schneider, Roger J. P. Dawson, Poul Nissen
Summary: This study utilized synthetic single-domain antibodies and serial synchrotron crystallography to determine the structure of GlyT1 in complex with an inhibitor, revealing that the inhibitor locks GlyT1 in an inward-open conformation and binds at the intracellular gate of the release pathway. These findings define the mechanism of inhibition and provide insights for the rational design of new, clinically efficacious GlyT1 inhibitors.
Article
Chemistry, Medicinal
Yuguang Zhao, Fredrik Svensson, David Steadman, Sarah Frew, Amy Monaghan, Magda Bictash, Tiago Moreira, Rod Chalk, Weixian Lu, Paul Fish, E. Yvonne Jones
Summary: Notum inhibitors can restore Wnt signaling which may be therapeutic for diseases such as osteoporosis and Alzheimer's. A novel class of covalent Notum inhibitors, 4-(indolin-1-yl)-4oxobutanoate esters, and their covalent adduct formation mechanisms were identified. Insights into the inhibition of Notum catalysis could lead to the development of more potent inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Endocrinology & Metabolism
Brice Beinsteiner, Isabelle M. L. Billas, Dino Moras
Summary: Hepatocyte Nuclear Factor 4 (HNF4) is a transcription factor that plays a crucial role in regulating liver-specific gene expression. Dysregulation of HNF4 is associated with human diseases like type I diabetes and hemophilia. This review focuses on the structures of HNF4 and its impact on the receptor's structure-function relationship.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Wolfram Seifert-Davila, Mathias Girbig, Luis Hauptmann, Thomas Hoffmann, Sebastian Eustermann, Christoph W. Mueller
Summary: Transcription factor (TF) IIIC recruits RNA polymerase (Pol) III to target genes by recognizing intragenic A- and B-box motifs. Cryo-electron microscopy structures revealed that the tau B module of TFIIIC recognizes the B-box through DNA shape and sequence readout. TFIIIC220 acts as a linker connecting the tau A and tau B subcomplexes, facilitating scanning for A-boxes and Pol III activation by TFIIIB.
Article
Biochemistry & Molecular Biology
Christopher J. Gisriel, David A. Flesher, Gaozhong Shen, Jimin Wang, Ming-Yang Ho, Gary W. Brudvig, Donald A. Bryant
Summary: Some cyanobacteria can use far-red light for photosynthesis. The study identified the specific binding sites of chlorophyll f in photosystem I and revealed structural differences in far-red light-acclimated cyanobacteria.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Yuyuan Zheng, Lei Ding, Xianhui Meng, Meg Potter, Alison L. Kearney, Jie Zhang, Jie Sun, David E. James, Guang Yang, Chun Zhou
Summary: Research has revealed that SIN1 is a vital component of mTORC2 and can interact with Ras family small GTPases through its Ras-binding domain (RBD). The association between Ras and SIN1/mTORC2 can potentially impact both mTORC2 and Ras-ERK pathways. By determining the high-resolution structures of HRas/KRas-SIN1 RBD complexes, researchers have identified the detailed interaction interface. Mutations in critical interface residues disrupt the Ras-SIN1 interaction, and in SIN1 knockout cells, it has been shown that the Ras-SIN1 association promotes SGK1 activity but inhibits insulin-induced ERK activation. Comparison with other Ras-binding proteins and experimental assays suggest that the association between HRas and SIN1 RBD is weaker than HRas-Raf1 RBD but slightly stronger than HRas-PI3K RBD, potentially explaining the different outcomes of insulin or EGF stimulation. Additionally, a Ras dimerization interface critical for Ras oligomerization has been uncovered. These findings contribute to our understanding of the Ras-SIN1 association and the cross-talk between growth factor-stimulated pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Masakazu Sugishima, Junichi Taira, Tatsuya Sagara, Ryota Nakao, Hideaki Sato, Masato Noguchi, Keiichi Fukuyama, Ken Yamamoto, Takuo Yasunaga, Hiroshi Sakamoto
Article
Biochemistry & Molecular Biology
Julia S. Kirpich, Che-Wei Chang, Jasper Franse, Qinhong Yu, Francisco Velazquez Escobar, Adam J. Jenkins, Shelley S. Martin, Rei Narikawa, James B. Ames, J. Clark Lagarias, Delmar S. Larsen
Summary: This study compares the photodynamics of two closely related red/green CBCRs, showing that they have comparable quantum yields for initiating reactions and unique features in their reverse dynamics. The research supports the conclusion that sequence similarity is useful for predicting pathways of light-induced evolution and quantum yield generation within subfamilies of CBCRs.
Article
Biochemistry & Molecular Biology
Sakiko Sato, Yumeka Matsushima, Miaki Kanazawa, Naoyuki Tanaka, Takashi Fujishiro, Kouhei Kunichika, Ryosuke Nakamura, Hiroaki Tomioka, Kei Wada, Yasuhiro Takahashi
Summary: IscU plays a central role in Fe-S cluster assembly and transfer, with potential for bypassing the essential roles of HscA and HscB through conformational interconversion. The study reveals dynamic conformational changes in IscU, highlighting the fundamental requirement for Fe-S cluster assembly and transfer.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hideaki Sato, Masakazu Sugishima, Mai Tsukaguchi, Takahiro Masuko, Mikuru Iijima, Mitsunori Takano, Yoshiaki Omata, Kei Hirabayashi, Kei Wada, Yoshio Hisaeda, Ken Yamamoto
Summary: HMBS plays a role in the heme biosynthesis pathway by using PBG derivatives in enzyme kinetic studies. Crystal structure analysis reveals the detailed reaction mechanism where four PBG molecules are covalently bound to create a hexapyrrole chain consecutively.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Kouhei Kunichika, Ryosuke Nakamura, Takashi Fujishiro, Yasuhiro Takahashi
Summary: The study determined the crystal structure of IscU from Methanothrix thermoacetophila, revealing a dimer structure with two [2Fe-2S] clusters in a specific arrangement. It was confirmed that two adjacent [2Fe-2S] clusters can be converted to a [4Fe-4S] cluster via reductive coupling in solution, with His106 identified to play a functional role in this process.
Article
Multidisciplinary Sciences
Weiqing Zhang, Robert D. Willows, Rui Deng, Zheng Li, Mengqi Li, Yan Wang, Yunling Guo, Weida Shi, Qiuling Fan, Shelley S. Martin, Nathan C. Rockwell, J. Clark Lagarias, Deqiang Duanmu
Summary: The biosynthesis of chlorophyll and heme in oxygenic phototrophs follows a common pathway that diverges with the insertion of magnesium or iron. The interaction of bilins with GENOMES UNCOUPLED 4 (GUN4) stimulates the enzymatic activity of magnesium chelatase (MgCh) and stabilizes the accumulation of protoporphyrin IX-binding CrCHLH1 subunit of MgCh. GUN4: bilin complexes play dual regulatory roles in sustaining bilin biosynthesis and chlorophyll biosynthesis in illuminated oxic environments of all photosynthetic eukaryotes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Sepalika Bandara, Nathan C. Rockwell, Xiaoli Zeng, Zhong Ren, Cong Wang, Heewhan Shin, Shelley S. Martin, Marcus Moreno, J. Clark Lagarias, Xiaojing Yang
Summary: The study focused on the crystal structure of a far-red-sensing subfamily of CBCRs, revealing interactions between the protein and chromophore that lead to a bathochromic shift due to two distinct red-shift mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Plant Sciences
Matthew Blain-Hartung, Nathan C. Rockwell, J. Clark Lagarias
Summary: CBCRs are a group of spectrally diverse photosensors that show potential for optogenetic applications, regulating the production of cyclic nucleotide second messengers associated with various bacterial physiological activities. Natural diversity generates promising candidates for broad spectrum optogenetic applications in live cells.
Article
Biochemistry & Molecular Biology
Ryosuke Nakamura, Shoko Ogawa, Yasuhiro Takahashi, Takashi Fujishiro
Summary: This study investigated the inhibition mechanisms of SufS by D-cycloserine (DCS) and L-cycloserine (LCS), and found that they act through different mechanisms and result in different products. The study also identified the importance of key residues in the inhibition mechanisms through the investigation of SufS variants. These findings provide valuable insights for the structure-based design of new drugs targeting SufS.
Article
Multidisciplinary Sciences
Nathan C. Rockwell, Shelley S. Martin, J. Clark Lagarias
Summary: Terrestrial ecosystems and human societies have relied on oxygenic photosynthesis since approximately 2.5 billion years ago. Cyanobacteria, the earliest known organisms to carry out oxygenic photosynthesis, use phycobiliproteins as light-harvesting antennae. The pathway for synthesizing phycobiliproteins involves the conversion of heme into PCB by heme oxygenase and the subsequent conversion of BV into PCB by FDBR PcyA. This study explores the origins of this pathway and finds that PcyA evolved from pre-PcyA proteins found in nonphotosynthetic bacteria. It is proposed that PcyA and phycobiliproteins originated in heterotrophic, nonphotosynthetic bacteria and were later acquired by cyanobacteria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Bo Larsen, Roberto Hofmann, Ines S. Camacho, Richard W. Clarke, J. Clark Lagarias, Alex R. Jones, Alexander M. Jones
Summary: Highlighter is a synthetic, light-gated gene expression system developed for plants. It allows unprecedented spatiotemporal control of target gene expression by guiding differential fluorescent protein expression in neighboring cells using light. The system has been used for optogenetic control over plant immunity and pigment production.
Article
Multidisciplinary Sciences
Nathan C. Rockwell, J. Clark Lagarias
Summary: Photosynthesis relies on chlorophylls synthesized via a common pathway, and the first step is the insertion of magnesium into protoporphyrin IX by magnesium chelatase. Oxygenic photosynthetic organisms require mechanisms to protect magnesium chelatase, and the protein GUN4 has been proposed to serve this role by binding to tetrapyrroles. Through comparative analysis and biochemical validation, it is suggested that GUN4 proteins binding to tetrapyrroles emerged early in cyanobacterial evolution as an adaptation for maintaining chlorophyll biosynthesis in the presence of light and oxygen.
Article
Biochemistry & Molecular Biology
Nathan C. Rockwell, Marcus Moreno, Shelley S. Martin, J. Clark Lagarias
Summary: Photoreceptors in the phytochrome superfamily and cyanobacteriochromes undergo photoconversion through chromophore isomerization, and protein-chromophore interactions control the fate of excited-state population.
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
(2022)
Meeting Abstract
Chemistry, Multidisciplinary
M. Sugishima, J. Taira, M. Iijima, H. Sato, K. Wada, M. Noguchi, K. Fukuyama, M. Takano, H. Sakamoto, K. Yamamoto
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2021)
Article
Plant Sciences
Wei Hu, Rosa Figueroa-Balderas, Cecilia Chi-Ham, J. Clark Lagarias