Article
Biochemistry & Molecular Biology
Jenna Hoersten, Gloria Ruiz-Gomez, Felix Lansing, Teresa Rojo-Romanos, Lukas Theo Schmitt, Jan Sonntag, M. Teresa Pisabarro, Frank Buchholz
Summary: This study discovers that paired mutations targeting residues involved in catalysis can create simple and obligate tyrosine site-specific recombinase (SSR) systems, where catalytic activity is dependent on the binding of all distinct subunits as a heterotetramer. This research improves the recombination specificity of designer-recombinases for therapeutic targets and enhances our understanding of SSR catalysis.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Milica Jelicic, Lukas Theo Schmitt, Maciej Paszkowski-Rogacz, Angelika Walder, Nadja Schubert, Jenna Hoersten, Duran Sueruen, Frank Buchholz
Summary: This study develops a systematic computational workflow for annotating putative tyrosine-type site-specific recombinase (Y-SSR) systems and identifies and characterizes eight new naturally occurring Cre-type SSR systems. The activity of these systems is tested in bacterial and mammalian cells, and selectivity profiles are established for both new and established Cre-type SSRs. Potential pseudo-sites and off-targets for Y-SSRs in the human and mouse genome are also identified, providing valuable information for future genome surgery applications.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Carla Guillen-Pingarron, Pedro M. Guillem-Gloria, Anjali Soni, Gloria Ruiz-Gomez, Martina Augsburg, Frank Buchholz, Massimiliano Anselmi, M. Teresa Pisabarro
Summary: Protein intrinsically disordered regions (IDRs) play crucial roles in molecular recognition and regulation. By investigating the disordered N-terminal tail of Cre enzyme, the study provides mechanistic insights into the relationship between structural disorder and protein function. The findings offer new understanding of the functional implications of IDRs and their potential applications in biotechnology and genomic medicine.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemical Research Methods
Wouter van Bergen, Johannes F. Hevler, Wei Wu, Marc P. Baggelaar, Albert J. R. Heck
Summary: Most drugs target proteins, and determining the exact drug binding sites on proteins is crucial for understanding their effects. A strategy called PhosID-ABPP was developed to identify drug binding sites using immobilized metal-affinity chromatography and phosphonate affinity tags. This method successfully identified over 500 unique binding sites of the drug PF-06672131. PhosID-ABPP also revealed differences in binding sites between intact cells and cell lysates, and captured a previously elusive binding site on the epidermal growth factor receptor.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Chemistry, Multidisciplinary
Zhian Hu, Jinlei Yang, Fujian Xu, Gongwei Sun, Xingyu Pan, Mengchan Xia, Sichun Zhang, Xinrong Zhang
Summary: The study discovered that myeloperoxidase can accurately cleave phosphorothioate-modified DNA to activate DNA machines for specific functions. This tool enables robust imaging of oxidative stress in living cells, providing a new approach for research on biostimuli and construction of DNA molecular devices.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Yasuyuki Matoba, Kosuke Oda, Yoshimi Muraki, Taro Masuda
Summary: The study showed that the presence of metallochaperone caddie protein (Cad) enables tyrosinase (Ty) to catalyze the catecholase reaction more effectively than the phenolase reaction. Mutations at the N191 residue can decrease the inherent ratio of phenolase versus catecholase activity. The increased basicity of the water molecule may be necessary for inhibiting the proton transfer in the catalytic cycle.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Yue Wang, Ries J. Langley, Kyle Tamshen, Julia Harms, Martin J. Middleditch, Heather D. Maynard, Stephen M. F. Jamieson, Jo K. Perry
Summary: The study successfully generated a novel PEGylated GHR antagonist by site-specific attachment of mPEG maleimide at an introduced cysteine residue, effectively reducing serum IGF-I levels in vivo.
Article
Chemistry, Medicinal
Naiem Ahmad Wani, Elad Stolovicki, Daniel Ben Hur, Yechiel Shai
Summary: In this study, a site-specific approach was used to modify antimicrobial peptides (AMPs), resulting in improved antimicrobial activity, resistance to proteolytic degradation, and reduced toxicity and hemolytic activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Matthew T. N. Yarnall, Eleonora I. Ioannidi, Cian Schmitt-Ulms, Rohan N. Krajeski, Justin Lim, Lukas Villiger, Wenyuan Zhou, Kaiyi Jiang, Sofya K. Garushyants, Nathaniel Roberts, Liyang Zhang, Christopher A. Vakulskas, John A. I. I. I. I. Walker, Anastasia P. Kadina, Adrianna E. Zepeda, Kevin Holden, Hong Ma, Jun Xie, Guangping Gao, Lander Foquet, Greg Bial, Sara K. Donnelly, Yoshinari Miyata, Daniel R. Radiloff, Jordana M. Henderson, Andrew Ujita, Omar O. Abudayyeh, Jonathan S. Gootenberg
Summary: The study presents a method called PASTE, which allows programmable integration of large and diverse DNA cargo into the genome. This method successfully integrated sequences up to 36 kilobases in length at multiple genomic loci, and demonstrated activity in non-dividing cells and in vivo.
NATURE BIOTECHNOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Holly E. Morgan, W. Bruce Turnbull, Michael E. Webb
Summary: Site-specific protein modification is a widely-used biochemical tool, but there are challenges in its development. This review focuses on the engineering of peptide ligases and their substrates to address these challenges, and explores techniques to improve reaction efficiency and expand substrate scope.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Chemistry, Inorganic & Nuclear
Julia Joekel, Frauke Nyssen, Daniel Siegmund, Ulf-Peter Apfel
Summary: The study reports the synthesis of an asymmetric hexa-amine cryptand analogue by selectively exchanging three of the secondary amines of one binding site with sulphur atoms, allowing for the formation of stable dinuclear complexes of metals with different oxidation numbers.
DALTON TRANSACTIONS
(2021)
Article
Multidisciplinary Sciences
Diane T. Takahashi, Daniele Gadelle, Keli Agama, Evgeny Kiselev, Hongliang Zhang, Emilie Yab, Stephanie Petrella, Patrick Forterre, Yves Pommier, Claudine Mayer
Summary: In this study, the structure of archaeal CsTOP1 in the absence of DNA was solved, revealing an open conformation resulting from a rotation between the CAP and CAT modules. The flexibility of the hinge, a five-residue loop connecting these modules, allows the opening/closing of the enzyme and the entry of DNA. A conserved tyrosine near the hinge was identified as mediating the transition from the open to closed conformation upon DNA binding.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Mainak Ghosh, Arka Bandyopadhyay, Suman Chowdhury, Debnarayan Jana
Summary: The research presented the successful realization of non-honeycomb lattice phagraphene in 1D form and demonstrated the emergence and stability of Dirac fermions through lattice renormalization. Additionally, the study explored the criteria for band gap opening in Dirac systems and the contributions of specific lattice sites to the formation of Dirac cones.
APPLIED SURFACE SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Davide Michieletto, Yair A. G. Fosado, Elias Melas, Marco Baiesi, Luca Tubiana, Enzo Orlandini
Summary: This study explores how type 2 Topoisomerase (TopoII) proteins enhance the relaxation of DNA molecules by speeding up the topological search and optimizing the sampling of the topological space. The findings suggest that the time scale of topological relaxation is independent of the substrate length. These results are significant for understanding the role of DNA topological simplification in vitro and in vivo.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Physical
Zongfang Wu, Fang Wang, Guanghui Sun, Feng Xiong, Botao Teng, Weixin Huang
Summary: This study demonstrates the high selectivity of Au catalysts in the hydrogenation of C2H2, especially at the step sites on the surface, where C2H2 is selectively semi-hydrogenated to C2H4 with 100% selectivity.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Xuemin Chen, Yanxiang Cui, Robert B. Best, Huaibin Wang, Z. Hong Zhou, Wei Yang, Martin Gellert
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2020)
Review
Biochemistry & Molecular Biology
Yang Gao, Wei Yang
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Woo Suk Choi, Peng He, Arti Pothukuchy, Jimmy Gollihar, Andrew D. Ellington, Wei Yang
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
Xuemin Chen, Xiang Xu, Yun Chen, Joyce C. Cheung, Huaibin Wang, Jiansen Jiang, Natalia de Val, Tara Fox, Martin Gellert, Wei Yang
Summary: This study reports cryo-EM structures of DNA-PK in both inactive and activated forms bound to DNA end or complexed with Ku70/80 and DNA, revealing the sequential transition of DNA-PK from inactive to activated forms. Activation of the kinase involves unprecedented stretching and twisting within individual solenoid segments, indicating a general regulatory mechanism of HEAT-repeat proteins.
Article
Biochemistry & Molecular Biology
Woo Suk Choi, Bochao Liu, Zhiyuan Shen, Wei Yang
Summary: BCCIP was isolated based on its interactions with tumor suppressors BRCA2 and p21, and deficiency of BCCIP resulted in embryonic lethality in mice with impaired cell proliferation and chromosome instability. Structurally, BCCIP is similar to GCN5-related acetyltransferases (GNATs) but with different sequence motifs, and it may have potential binding sites for partner proteins and enzymatic activity.
Article
Cell Biology
Janice Ortega, Grace Sanghee Lee, Liya Gu, Wei Yang, Guo-Min Li
Summary: The study reveals that the sliding of MutS alpha is necessary for mismatch removal in MMR, MutS alpha recruits MutL alpha to form a mismatch-bound complex and initiates MMR by nicking the daughter strand 5' to the mismatch, Exo1 conducts excision, solving the mechanism of MMR initiation and mispair removal.
Article
Biochemistry & Molecular Biology
Alexandra Vaisman, Krystian Lazowski, Martin A. M. Reijns, Erin Walsh, John P. McDonald, Kristiniana C. Moreno, Dominic R. Quiros, Marlen Schmidt, Harald Kranz, Wei Yang, Karolina Makiela-Dzbenska, Roger Woodgate
Summary: The Escherichia coli dnaE gene encodes the alpha-catalytic subunit of DNA polymerase III, with the study focusing on the role of residues H760 and S759 in maintaining genome stability. Out of 38 mutants created, only nine were successfully sub-cloned, with three having substitutions at H760 and six having substitutions at S759. Further characterization revealed altered phenotypes in terms of deoxyribonucleotide base selectivity and ribonucleotide discrimination for certain alleles.
MOLECULAR MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Mark T. Gregory, Yang Gao, Qiang Cui, Wei Yang
Summary: Through mutagenesis and structural analysis, researchers delineated the entities surrounding the nucleophile 3'-OH in the reaction catalyzed by DNA polymerase Pol eta, revealing details of the deprotonation process. The study found that the conserved S113 residue stabilizes the primer end by forming a hydrogen bond with the primer 3'-OH in the ground state, and mutation of S113 to alanine reduces catalytic efficiency.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Ayslan Castro Brant, Wei Tian, Vladimir Majerciak, Wei Yang, Zhi-Ming Zheng
Summary: SARS-CoV-2 is a highly contagious respiratory virus causing adult atypical pneumonia COVID-19 with severe acute respiratory syndrome (SARS). This virus enters susceptible cells and directly translates polyproteins to initiate viral genome replication and transcription.
CELL AND BIOSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Xuemin Chen, Martin Gellert, Wei Yang
Summary: RAG is an RNH-type DNA recombinase evolved to initiate V(D)J gene rearrangement, with crystal structure and biochemical studies shedding light on its evolution from an ordinary transposase to a specialized recombinase.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lan Liu, Xuemin Chen, Jun Li, Huaibin Wang, Christopher J. Buehl, Noah J. Goff, Katheryn Meek, Wei Yang, Martin Gellert
Summary: DNA-PK plays a dual role in DNA damage repair by protecting and processing broken DNA ends. The type of DNA ends regulates the kinase activity and autophosphorylation of DNA-PK, which in turn coordinate non-homologous end joining (NHEJ) events.
Article
Multidisciplinary Sciences
Woo Suk Choi, Peter J. Weng, Wei Yang
Summary: Telomerase synthesizes telomeres at the ends of linear chromosomes by reverse transcription from a short RNA template. In this study, the potential of the structural cavity of tcTERT to accommodate a looped-out DNA bulge and enable the separation of the RNA/DNA hybrid was investigated. It was found that tcTERT can accommodate and extend a looped-out telomeric repeat in the DNA primer, but retroviral reverse transcriptase cannot. The ternary-complex structure of tcTERT with a downstream RNA/DNA hybrid was also determined, and it was shown to enhance the efficiency of telomere synthesis by tcTERT. Overall, flexible RNA-DNA binding plays a crucial role in telomeric repeat addition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Xi Yang, Sourav Saha, Wei Yang, Keir C. Neuman, Yves Pommier
Summary: This study elucidates the biochemical mechanisms of human TOP3B, highlighting its differential roles in DNA and RNA catalysis, as well as the impact of regulatory factors on its catalytic performance.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Christopher J. Buehl, Noah J. Goff, Steven W. Hardwick, Martin Gellert, Tom L. Blundell, Wei Yang, Amanda K. Chaplin, Katheryn Meek
Summary: Non- homologous end joining is the main pathway for repairing double-strand breaks in mammals. DNA-PK plays a central role in orchestrating multiple steps in non- homologous end joining. Recent structural studies have revealed two distinct NHEJ complexes that mediate the synapsis of DNA ends. One complex involves a DNA-PK dimer mediated by XLF, while the other complex forms through a domain-swap mechanism involving interaction between the C terminus of Ku80 from one DNA-PK protomer and another DNA-PK protomer. The distance between the synapsed DNA ends in both complexes is the same, suggesting a conserved long-range synaptic complex. A mutational strategy has shown that these two dimers have distinct cellular functions, with one promoting fill-in end processing and the other promoting DNA end resection. The specific DNA-PK dimer formed determines the mechanism by which the ends can be ligated, and this may be influenced by the structure of the DNA ends.
Article
Multidisciplinary Sciences
Jinseok Kim, Chia-Lung Li, Xuemin Chen, Yanxiang Cui, Filip M. Golebiowski, Huaibin Wang, Fumio Hanaoka, Kaoru Sugasawa, Wei Yang
Summary: Nucleotide excision repair is responsible for removing DNA lesions caused by ultraviolet light, cisplatin-like compounds, and bulky adducts. This study reveals the structures of human XPC recognizing DNA lesions and transferring them to the TFIIH core complex for verification and further repair.