Article
Biochemical Research Methods
Jack B. Greisman, Kevin M. Dalton, Candice J. Sheehan, Margaret A. Klureza, Igor Kurinov, Doeke R. Hekstra
Summary: Single-wavelength anomalous diffraction (SAD) is a common method for solving the phase problem in macromolecular structures. This study presents a strategy to obtain high-quality data from room-temperature, single-crystal experiments, and successfully applies it to solve four structures of three model systems. The resulting data sets allow for automatic phasing and model building, and reveal alternate conformations of proteins at room temperature.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sunbin Deng, Jiaxi Cai, Stephen C. Harrison, Huilin Zhou, Stephen M. Hinshaw
Summary: Successful mitosis relies on the correct attachment of chromosomes to microtubules. The kinetochore plays a crucial role in this process by recognizing specific chromatin and ensuring the formation of only one kinetochore per chromatid at the correct location. The crystal structure of the Cse4 peptide bound to the inner kinetochore Okp1-Ame1 complex provides insights into centromere recognition and the organization of the inner kinetochore.
Article
Biochemistry & Molecular Biology
Gabriel Javitt, Alisa Kinzel, Nava Reznik, Deborah Fass
Summary: Zymogen granule membrane protein 16 (ZG16) is a protein produced in organs that secrete enzymes and other proteins into the digestive tract, with the ability to bind microbial pathogens. The CXXC motif on ZG16 contributes to its activity, and can be oxidized by specific enzymes to engage in redox reactions.
Article
Nanoscience & Nanotechnology
Alejandro Prieto-Castaneda, Siseth Martinez-Caballero, Antonia R. Agarrabeitia, Inmaculada Garcia-Moreno, Santiago de la Moya, Maria J. Ortiz, Juan A. Hermoso
Summary: The study introduces a ytterbium(III) complex as a phasing agent for de novo protein structure determination at approximately 1 A, offering high phasing power and high-quality electron density maps while maintaining crystallographic resolution. This agent presents a new possibility for X-ray crystallography of complex biomacromolecules.
ACS APPLIED BIO MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Xiuxiu Ma, Meng Wang, Fan Wang, Jiao Li, Zhengguang Zhang, Jiapeng Zhu, Bing Liu
Summary: In this study, a small-molecule BRD4 inhibitor named compound 3 was identified as an effective inhibitor of BRD4 activity. Co-crystal structure analysis revealed that compound 3 occupies the KAc recognition pockets of BRD4 by forming key hydrogen bonds with Asn140 and engaging in hydrophobic interactions, thereby hindering the binding of acetylated lysine to BRD4. These findings suggest that compound 3 can serve as a lead compound for the development of structurally novel BRD4 inhibitors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Multidisciplinary Sciences
Yihu Xie, Christopher L. Lord, Bradley P. Clarke, Austin L. Ivey, Pate S. Hill, W. Hayes McDonald, Susan R. Wente, Yi Ren
Summary: CTDK-1 is the primary RNA Pol II CTD Ser2 kinase complex in budding yeast, consisting of a CDK Ctk1, a cyclin Ctk2, and a unique subunit Ctk3 which activates Ctk1 by stabilizing the T-loop. Additionally, Ctk3 contributes to the assembly of CTDK-1 through interactions with both Ctk1 and Ctk2, and physically interacts with Gbp2, a serine/arginine-like protein. These findings reveal a regulatory mechanism of CDK complexes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Alena Kroupova, Fabian Ackle, Igor Asanovic, Stefan Weitzer, Franziska M. Boneberg, Marco Faini, Alexander Leitner, Alessia Chui, Ruedi Aebersold, Javier Martinez, Martin Jinek
Summary: RtcB enzymes are RNA ligases that are essential for various cellular processes, including tRNA splicing and RNA repair. In metazoa, RtcB functions as part of a larger tRNA ligase complex, with different subunits playing crucial roles in maintaining complex integrity. The crystal structures of key subunits provide insights into the catalytic mechanism and molecular architecture of the human tRNA ligase complex, shedding light on its functions in cellular RNA metabolism.
Article
Multidisciplinary Sciences
Lijing Su, Muhammad Athamna, Ying Wang, Junmei Wang, Marina Freudenberg, Tao Yue, Jianhui Wang, Eva Marie Y. Moresco, Haoming He, Tsaffrir Zor, Bruce Beutler
Summary: Sulfatides can activate mouse immune responses via the TLR4-MD-2 complex, but exhibit antagonistic effects in human cells. Their activity is related to the presence of the sulfate group and the length of the fatty acid chain, and their structure mimics the activation mechanism of molecules like LPS in receptors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Luke E. Formosa, Shadi Maghool, Alice J. Sharpe, Boris Reljic, Linden Muellner-Wong, David A. Stroud, Michael T. Ryan, Megan J. Maher
Summary: COA7 is a crucial assembly factor for the biogenesis of mitochondrial complex IV. It interacts with SCO1 and SCO2 to catalyze copper relay and reduction of disulfide bonds, which are important for complex IV assembly.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Hyun-Jong Eun, Jooyeon Lee, Su-Jin Kang, Bong-Jin Lee
Summary: Toxin and Antitoxin systems are crucial for bacterial survival against harsh environments like antibiotic treatments, with the VapBC system being the most abundant among them in Mycobacterium tuberculosis. The VapBC43 system, related to vancomycin treatment response, features a structure where a single VapB43 molecule binds to a VapC43 dimer. Despite lacking conserved acidic residues, VapC43 exhibits ribonuclease activity, and its structural information may aid in developing inhibitors for use as adjuvants in vancomycin therapy against M. tuberculosis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Richard Lawrence Kingston, Rick P. Millane
Summary: The procedure describes a method for direct phase determination in protein crystallography, solving the problem by seeking an image consistent with both the diffraction data and constraints on the density distribution in the crystal. It uses an iterative projection algorithm, the Difference Map algorithm, and breaks down the problem into two stages to improve computational efficiency, with the algorithm initiated with multiple phase sets for consistent results.
Article
Biochemistry & Molecular Biology
Maria Raics, Alex Kalman Balogh, Chandan Kishor, Istvan Timari, Francisco J. Medrano, Antonio Romero, Rob Marc Go, Helen Blanchard, Laszlo Szilagyi, Katalin E. Kover, Krisztina Feher
Summary: In this study, the binding affinities of two selenium-containing hGal-3 inhibitors to hGal-3 were investigated using NMR spectroscopy and fluorescence anisotropy titrations. The results showed that these derivatives bind to hGal-3 at a specific site, but with weaker interaction strength.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mariana Abrahao Bueno Morais, Joice Helena Paiva, Mario Tyago Murakami
Summary: Carbohydrate-binding modules (CBMs) are independently folded domains associated with carbohydrate-active enzymes (CAZymes). The high-resolution SAD-solved structure of a CBM from family 3 (BsCBM3) that binds to crystalline cellulose is reported, showing molecular plasticity and structural differences between crystalline forms. Variations in the cellulose binding interface were observed, supporting the idea that family 3 CBMs are structurally dynamic and suggesting a role in polysaccharide recognition and enzyme activity modulation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Physics, Applied
Jong Woo Kim, Mathew J. Cherukara, Ashish Tripathi, Zhang Jiang, Jin Wang
Summary: Coherent surface scattering imaging requires a mathematical conversion to visualize specimen structures, which can now be predicted using a deep learning neural network model to instantly obtain results from scattering patterns. This is highly beneficial for both experimental effectiveness and data analysis.
APPLIED PHYSICS LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Cen Chen, Ziyuan Fang, Zhen Huang
Summary: Crystallization phasing and obtaining high-quality crystals are major challenges for X-ray crystallographic analysis of nucleic acids. In this study, the authors addressed these challenges by incorporating selenium atoms into DNA duplexes, which resulted in larger and higher quality crystals compared to standard DNA crystals. These findings provide a simple strategy to overcome crystallization challenges in nucleic acid crystallography.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Biochemistry & Molecular Biology
Hayato Ozaki, Takuya Asano, Hide-Nori Tanaka, Naoko Komura, Hiromune Ando, Hideharu Ishida, Akihiro Imamura
Summary: This paper reports the chemical synthesis of polylactosamine fragments up to 22-mer using a blockwise synthetic approach. The synthesis of an octasaccharide of keratan sulfate glycan was achieved using large building blocks as glycosyl donors and acceptors. The coupling reaction between these building blocks facilitated the purification of glycosylated products.
CARBOHYDRATE RESEARCH
(2022)
Editorial Material
Biochemistry & Molecular Biology
Tatsuya Suzuki
TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Kaiming Zhang, Naoki Horikoshi, Shanshan Li, Alexander S. Powers, Mikhail A. Hameedi, Grigore D. Pintilie, Hee-Don Chae, Yousuf A. Khan, Carl-Mikael Suomivuori, Ron O. Dror, Kathleen M. Sakamoto, Wah Chiu, Soichi Wakatsuki
Summary: In this study, a protein double shell was engineered to overcome the size limitation of determining structures of flexible proteins smaller than 30 kDa. This approach successfully determined the structure of the 11 kDa KIX domain of CBP, and molecular dynamics simulations were used to design peptides that block protein-protein interactions. The findings provide insights for the development of next-generation inhibitors.
ACS CENTRAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Irimpan I. Mathews, Naoki Horikoshi, Tsutomu Matsui, Manat Kaur, Soichi Wakatsuki, Daria Mochly-Rosen, Adriana Ann Garcia
Summary: This study identified a small molecule that activates G6PD variants by stabilizing the allosteric NADP(+) and dimer complex, suggesting potential therapeutic strategies for G6PD deficiency. The connection between allosteric NADP+ binding, oligomerization, and pathogenicity was elucidated, and stabilizing the dimer and tetramer was found to improve protein stability and activity. These findings provide a foundation for future drug discovery efforts.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Hasan DeMirci, Yashas Rao, Gabriele M. Stoffel, Bastian Vogeli, Kristina Schell, Aharon Gomez, Alexander Batyuk, Cornelius Gati, Raymond G. Sierra, Mark S. Hunter, E. Han Dao, Halil Ciftci, Brandon Hayes, Fredric Poitevin, Po-Nan Li, Manat Kaur, Kensuke Tono, David Adrian Saez, Samuel Deutsch, Yasuo Yoshikuni, Helmut Grubmueller, Tobias J. Erb, Esteban Vohringer-Martinez, Soichi Wakatsuki
Summary: This study used various experimental methods to investigate the structural organization of ECR in Kitasatospora setae, and found that its catalytic activity is carried out by a pair of dimers. The results reveal the dynamic organization and synchronized inter- and intrasubunit communications of this enzyme during catalysis.
ACS CENTRAL SCIENCE
(2022)
Article
Biochemical Research Methods
Alexei S. Soares, Yusuke Yamada, Jean Jakoncic, Sean McSweeney, Robert M. Sweet, John Skinner, James Foadi, Martin R. Fuchs, Dieter K. Schneider, Wuxian Shi, Babak Andi, Lawrence C. Andrews, Herbert J. Bernstein
Summary: KAMO and BLEND are effective tools for managing the merging of large numbers of data sets in serial crystallography. By extending BLEND to support additional clustering options and using more accurate distance metrics, it is possible to reduce the need for manual intervention in the process. This increases sensitivity to differences in unit-cell parameters and allows clustering to assemble nearly complete data sets based on intensity or amplitude differences.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Mikhail Ali Hameedi, Erica T. Prates, Michael R. Garvin, Irimpan Mathews, B. Kirtley Amos, Omar Demerdash, Mark Bechthold, Mamta Iyer, Simin Rahighi, Daniel W. Kneller, Andrey Kovalevsky, Stephan Irle, Van-Quan Vuong, Julie C. Mitchell, Audrey Labbe, Stephanie Galanie, Soichi Wakatsuki, Daniel Jacobson
Summary: The authors report on the crystallographic and computational studies that explain how SARS-CoV-2 3CLpro cleaves NF-kappa B Essential Modulator, a host protein, in addition to its viral substrates. They discuss the association between this cleavage and the high adaptability of SARS-CoV-2 in humans. The study provides insights into the binding mechanism between 3CLpro and NEMO, as well as the role of key binding residues in the fitness of SARS-CoV-2.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Eriko Yamaguchi, Naoko Komura, Hide-Nori Tanaka, Akihiro Imamura, Hideharu Ishida, Sophie Groux-Degroote, Martina Muehlenhoff, Kenichi G. N. Suzuki, Hiromune Ando
Summary: Ganglioside GD2 is involved in the proliferation and migration of breast cancer cells. However, its role is not well understood due to the difficulty in observing its dynamic and transient domains called lipid rafts in cell plasma membranes. In this study, we synthesized a fluorescent analog of GD2, which exhibits raft-philic characteristics, and can potentially assist in the investigation of raft-associated interactions using single-molecule imaging techniques.
GLYCOCONJUGATE JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Yuki Suganuma, Akihiro Imamura, Hiromune Ando, Makoto Kiso, Hiromu Takematsu, Takeshi Tsubata, Hideharu Ishida
Summary: We developed a new synthetic method for the large-scale synthesis of CD22-interacting glycans, which will facilitate the search for potential CD22 inhibitors with therapeutic potential.
GLYCOCONJUGATE JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Shogo Hamajima, Naoko Komura, Hide-Nori Tanaka, Akihiro Imamura, Hideharu Ishida, Tsuyoshi Ichiyanagi, Hiromune Ando
Summary: Chemical synthesis of Kdo-containing glycans is important for developing vaccines against pathogenic bacteria. The alpha-stereoselective glycosidation of Kdo has been achieved using a macrobicyclic donor. In this study, the protection of the 4-OH group and the use of a selectively removable booster allowed the synthesis of the dimeric Kdo sequence.
Article
Chemistry, Organic
Shogo Hamajima, Naoko Komura, Hide-Nori Tanaka, Akihiro Imamura, Hideharu Ishida, Haruka Noguchi, Tsuyoshi Ichiyanagi, Hiromune Ando
Summary: We describe a method for alpha-selective glycosidation of 3-deoxy-D-manno-2-octulosonic acid (Kdo) using a macrobicyclic Kdo donor as the precursor of a bridgehead oxocarbenium ion. The stereoselectivity of the reaction is not affected by the substrate structure and reaction conditions.
Article
Multidisciplinary Sciences
Nai-Chi Chen, Chun-Hsiung Wang, Masato Yoshimura, Yi-Qi Yeh, Hong-Hsiang Guan, Phimonphan Chuankhayan, Chien-Chih Lin, Pei-Ju Lin, Yen-Chieh Huang, Soichi Wakatsuki, Meng-Chiao Ho, Chun-Jung Chen
Summary: Understanding the structural diversity of honeybee-infecting viruses is crucial for protecting pollinator health and managing disease spread in ecology and agriculture. This study used cryo-EM to determine the structures of T=4 and T=3 capsids of Lake Sinai virus (LSV) 2 and delta-N48 LSV1. The analysis revealed unique structural features and interactions of the capsid proteins, as well as the impact of pH on capsid conformations and particle sizes.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Brian C. Sanders, Suman Pokhrel, Audrey D. Labbe, Irimpan I. Mathews, Connor J. Cooper, Russell B. Davidson, Gwyndalyn Phillips, Kevin L. Weiss, Qiu Zhang, Hugh O'Neill, Manat Kaur, Jurgen G. Schmidt, Walter Reichard, Surekha Surendranathan, Jyothi Parvathareddy, Lexi Phillips, Christopher Rainville, David E. Sterner, Desigan Kumaran, Babak Andi, Gyorgy Babnigg, Nigel W. Moriarty, Paul D. Adams, Andrzej Joachimiak, Brett L. Hurst, Suresh Kumar, Tauseef R. Butt, Colleen B. Jonsson, Lori Ferrins, Soichi Wakatsuki, Stephanie Galanie, Martha S. Head, Jerry M. Parks
Summary: Designed a series of protease inhibitors targeting SARS-CoV-2, with the most effective inhibitor capable of blocking viral replication in mammalian cells and showing no significant inhibition of human proteases. These findings present an opportunity for the development of protease inhibitors.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
James S. Davies, Michael J. Currie, Rachel A. North, Mariafrancesca Scalise, Joshua D. Wright, Jack M. Copping, Daniela M. Remus, Ashutosh Gulati, Dustin R. Morado, Sam A. Jamieson, Michael C. Newton-Vesty, Gayan S. Abeysekera, Subramanian Ramaswamy, Rosmarie Friemann, Soichi Wakatsuki, Jane R. Allison, Cesare Indiveri, David Drew, Peter D. Mace, Renwick C. J. Dobson
Summary: The researchers report the structure of the TRAP transporter and propose a model for substrate transport using an 'elevator-with-an-operator' mechanism.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Maina Takahashi, Naoko Komura, Yukako Yoshida, Eriko Yamaguchi, Ami Hasegawa, Hide-Nori Tanaka, Akihiro Imamura, Hideharu Ishida, Kenichi G. N. Suzuki, Hiromune Ando
Summary: Gangliosides, a type of glycosphingolipids, form dynamic structures with proteins in cell plasma membranes and play important roles in various biological processes. Using single-molecule imaging, we investigated the behavior of a lacto-series ganglioside and discovered its interactions with other important proteins.
RSC CHEMICAL BIOLOGY
(2022)
