Article
Chemistry, Multidisciplinary
Yugang Zhang, Dan Su, Boris Dzikovski, Sean H. Majer, Rachael Coleman, Siddarth Chandrasekaran, Michael K. Fenwick, Brian R. Crane, Kyle M. Lancaster, Jack H. Freed, Hening Lin
Summary: All radical-SAM enzymes require a [4Fe-4S](Cys)(3) cluster for activity, which is highly air-sensitive. A study on yeast Dph1-Dph2 revealed that the iron-containing protein Dph3 donates an iron atom to convert a [3Fe-4S] cluster to a functional [4Fe-4S] cluster, maintaining radical-SAM enzyme activity in aerobic environments.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Microbiology
Chu Wang, Christian Nehls, Dirk Baabe, Olaf Burghaus, Robert Hurwitz, Thomas Gutsmann, Martin Broering, Michael Kolbe
Summary: FliB is a SAM-dependent methyltransferase that enhances the adhesion and invasion ability of Salmonella by modifying flagellin. This study reveals the importance of the [4Fe-4S] cluster in FliB for the methylation reaction and its coordination by a cysteine-rich motif that is highly conserved among Enterobacteriaceae.
Article
Biology
Jonathan Fuchs, Rapolas Jamontas, Maren Hellen Hoock, Jonathan Oltmanns, Beatrice Golinelli-Pimpaneau, Volker Schuenemann, Antonio J. Pierik, Rolandas Meskys, Agota Aucynaite, Matthias Boll
Summary: This study reveals a new enzyme called TudS desulfidase in cells, which can desulfurize thiouracil and play a crucial role in recycling and detoxification of tRNA-derived 4-thiouridine monophosphate nucleosides for RNA synthesis.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Masato Ishizaka, Minghao Chen, Shun Narai, Yoshikazu Tanaka, Toyoyuki Ose, Masaki Horitani, Min Yao
Summary: Iron-sulfur (Fe-S) clusters play a vital role in enzyme activity. This study focuses on the relationship between the Fe-S cluster type and the catalytic activity of a tRNA-thiolation enzyme (TtuA). The researchers observed that [3Fe-4S]-TtuA spontaneously transforms into [4Fe-4S]-TtuA within minutes to an hour, and [3Fe-4S]-TtuA is highly inactive and unstable. These findings provide insights into the Fe-S cluster type used by the tRNA-thiolation enzyme.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nisha He, Jingjing Zhou, Ornella Bimai, Jonathan Oltmanns, Jean-Luc Ravanat, Christophe Velours, Volker Schuenemann, Marc Fontecave, Beatrice Golinelli-Pimpaneau
Summary: This study identified the TtuI enzymes involved in the sulfuration of bacterial and archaeal tRNAs and proposed a mechanism involving the transfer of sulfur atoms through the assembly of a [4Fe-4S] cluster coordinated by the CXXC + C motif.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Isabelle Fix, Lorenz Heidinger, Thorsten Friedrich, Gunhild Layer
Summary: In archaea and sulfate-reducing bacteria, heme is synthesized via the siroheme-dependent pathway. The Radical SAM enzyme AhbD catalyzes the last step of this pathway, converting iron-coproporphyrin III into heme. Amino acid sequence analysis and structural modeling suggested that some AhbD proteins may contain two auxiliary iron-sulfur clusters. Study on AhbD from Methanosarcina barkeri confirmed the presence of two auxiliary [4Fe-4S] clusters, and the clusters likely participate in the heme synthase activity.
Article
Chemistry, Multidisciplinary
Andrea Schmidt, Jacqueline Kalms, Christian Teutloff, Sagie Katz, Stefan Frielingsdorf, Rhiannon M. Evans, Johannes Fritsch, Elisabeth Siebert, Christian Teutloff, Fraser A. Armstrong, Ingo Zebger, Oliver Lenz, Patrick Scheerer
Summary: The membrane-bound [NiFe]-hydrogenase of Cupriavidus necator is an O-2-tolerant hydrogenase with a unique Cys(6)[4Fe-3S] cluster. Replacing two additional cysteines in the cluster led to structural changes and decreased O-2 tolerance. Formation of a hydroxy ligand in the active site under electron-deficient conditions can protect the enzyme from O-2 binding.
Article
Chemistry, Multidisciplinary
Binbin Gu, Bernd Goldfuss, Jeroen S. S. Dickschat
Summary: The second sesterterpene synthase from bacteria was identified in this study, which is the sesterviolene synthase from Streptomyces violens. Isotopic labelling experiments and DFT calculations were used to gain insights into its complex cyclisation mechanism. Through enzyme engineering via site-directed mutagenesis, a high-yielding enzyme variant was obtained that produced six additional minor products and the main product in sufficient quantities for chemistry studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
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
Chemistry, Multidisciplinary
Houchao Xu, Gregor Schnakenburg, Bernd Goldfuss, Jeroen S. Dickschat
Summary: In this study, a gene from Kitasatospora viridis encoding a terpene synthase homolog was cloned and expressed. The purified recombinant protein exhibited sesterterpene synthase activity, converting geranylfarnesyl diphosphate (GFPP) into sesterviridene A with a yield of 19%. Enzymatic conversions on a large scale allowed for the isolation of two side products with a very low yield of approximately 0.1%. Chemical transformations were employed to obtain derivatives of sesterviridene A, and their structures were confirmed by NMR-based structural assignments. The absolute configuration of sesterviridene A was determined using stereoselectively deuterated precursors and anomalous dispersion X-ray crystallography. The cyclisation mechanism from GFPP to sesterviridene A was extensively studied through isotopic labelling experiments and DFT calculations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Sicong Li, Priscila dos Santos Bury, Fanglu Huang, Junhong Guo, Guo Sun, Anna Reva, Chuan Huang, Xinyun Jian, Yuan Li, Jiahai Zhou, Zixin Deng, Finian J. Leeper, Peter F. Leadlay, Marcio V. B. Dias, Yuhui Sun
Summary: The study reveals the dideoxygenation process of intermediates JI-20A and JI-20B in gentamicin, starting with phosphorylation catalyzed by GenP and then modified by GenB3 and GenB4 to form gentamicin C complex. Insights into the catalytic mechanisms of GenB3 and GenB4 are provided through crystal structures and site-directed mutagenesis.
Article
Biochemistry & Molecular Biology
Elliot Corless, Syed Muhammad Saad Imran, Maxwell B. Watkins, John-Paul Bacik, Jenna R. Mattice, Angela Patterson, Karamatullah Danyal, Mark Soffe, Robert Kitelinger, Lance C. Seefeldt, Sofia Origanti, Brian Bennett, Brian Bothner, Nozomi Ando, Edwin Antony
Summary: In bacteriochlorophyll biosynthesis, the reduction of protochlorophyllide to chlorophyllide is catalyzed by dark-operative protochlorophyllide oxidoreductase. This process is regulated by ATP-induced conformational changes, and the flexible N-terminal region plays a role in autoinhibition. The release of this region upon ATP binding leads to specific conformational changes, promoting complex formation and protochlorophyllide reduction.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Carsten Schotte, Peer Lukat, Adrian Deuschmann, Wulf Blankenfeldt, Russell J. Cox
Summary: The non-canonical terpene cyclase AsR6 plays a crucial role in the biosynthesis of tropolone sesquiterpenoid xenovulene A and has a unique farnesyl diphosphate binding motif. Site-directed mutagenesis experiments revealed that a single residue, L285/M261, controls the production of different humulene isomers, with M261 having gatekeeping control over product formation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Kizerbo A. Taizoumbe, Simon T. Steiner, Jeroen S. Dickschat
Summary: The products and cyclization mechanism of the enzymes ScCotB2 and SiCotB2 were investigated through in vitro experiments and isotopic labeling.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Jinxiu Wang, Suze Ma, Wei Ding, Tuo Chen, Qi Zhang
Summary: The aminoglycoside antibiotic apramycin contains a unique bicyclic octose moiety, and biosynthesis of this moiety involves an oxidoreductase AprQ, which has a unique catalytic mechanism involving a four-electron oxidation in single turnover conditions. AprQ contains a flavin mononucleotide (FMN) cofactor, making it different from other known Q series enzymes, and is classified as a flavoprotein oxidase. This study expands the understanding of the catalytic mechanism of AprQ and the family of flavoprotein oxidases.
CHINESE JOURNAL OF CHEMISTRY
(2021)
Article
Biochemical Research Methods
Di Du, Lin Tan, Yumeng Wang, Bo Peng, John N. Weinstein, Fredric E. Wondisford, Xiaoyang Su, Philip L. Lorenzi
BMC BIOINFORMATICS
(2019)
Article
Gastroenterology & Hepatology
Lei Chen, Roshan P. Vasoya, Natalie H. Toke, Aditya Parthasarathy, Shirley Luo, Eric Chiles, Juan Flores, Nan Gao, Edward M. Bonder, Xiaoyang Su, Michael P. Verzi
Article
Chemistry, Analytical
Xiaoyang Su, Eric Chiles, Sara Maimouni, Fredric E. Wondisford, Wei-Xing Zong, Chi Song
ANALYTICAL CHEMISTRY
(2020)
Article
Cell Biology
Magdalena Dragan, Mai-Uyen Nguyen, Stephania Guzman, Cameron Goertzen, Muriel Brackstone, Waljit S. Dhillo, Paul R. Bech, Sophie Clarke, Ali Abbara, Alan B. Tuck, David A. Hess, Sharon R. Pine, Wei-Xing Zong, Frederic E. Wondisford, Xiaoyang Su, Andy V. Babwah, Moshmi Bhattacharya
CELL DEATH & DISEASE
(2020)
Article
Endocrinology & Metabolism
Yujue Wang, Hyokjoon Kwon, Xiaoyang Su, Fredric E. Wondisford
MOLECULAR METABOLISM
(2020)
Article
Cell Biology
Lifeng Yang, Juan Carlos Garcia Canaveras, Zihong Chen, Lin Wang, Lingfan Liang, Cholsoon Jang, Johannes A. Mayr, Zhaoyue Zhang, Jonathan M. Ghergurovich, Le Zhan, Shilpy Joshi, Zhixian Hu, Melanie R. McReynolds, Xiaoyang Su, Eileen White, Raphael J. Morscher, Joshua D. Rabinowitz
Article
Medicine, Research & Experimental
Juan Liu, Cen Zhang, Hao Wu, Xiao-Xin Sun, Yanchen Li, Shan Huang, Xuetian Yue, Shou-En Lu, Zhiyuan Shen, Xiaoyang Su, Eileen White, Bruce G. Haffty, Wenwei Hu, Zhaohui Feng
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Multidisciplinary Sciences
Sarah A. Skubel, Xiaoyang Su, Alexander Poulev, Llewellyn C. Foxcroft, Vyacheslav Dushenkov, Ilya Raskin
SCIENTIFIC REPORTS
(2020)
Review
Medicine, Research & Experimental
Yujue Wang, Sheng Hui, Fredric E. Wondisford, Xiaoyang Su
Summary: Metabolic flux analysis aims to reveal metabolic reaction rates using stable isotope labeling patterns. The latest EMU framework expanded to simulate tandem mass spectrometry data has improved the precision of MFA. Combining MIDs of parent and daughter ions with TMID for MFA is more powerful than using TMID alone.
LABORATORY INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Amanda Williams, Eric N. Chiles, Dennis Conetta, Jananan S. Pathmanathan, Phillip A. Cleves, Hollie M. Putnam, Xiaoyang Su, Debashish Bhattacharya
Summary: Understanding the response of coral holobionts to environmental changes, particularly coral bleaching caused by heat stress, is crucial for conservation efforts. Research has identified certain dipeptides as potential diagnostic markers for thermal stress in wild coral populations.
Article
Medicine, Research & Experimental
Yujue Wang, Lance R. Parsons, Xiaoyang Su
Summary: Stable isotope labeling techniques are widely used in metabolomics and proteomics, requiring accurate correction for isotope natural abundance and tracer isotopic impurity prior to quantitative analysis. AccuCor2 is an R-based tool developed for the correction of C-13-N-15 or C-13-H-2 labeling experiments, showing improved accuracy for dual-isotope tracer data. High mass resolution is crucial for resolving tracer isotopologues in such experiments.
LABORATORY INVESTIGATION
(2021)
Review
Biochemistry & Molecular Biology
Joyce Xu, Xiaoyang Su, Stephen K. Burley, X. F. Steven Zheng
Summary: SOD1 is a crucial antioxidant enzyme that converts superoxide to hydrogen peroxide and molecular oxygen. It is involved in maintaining cellular redox homeostasis and has been linked to various diseases. Recent studies have also highlighted its role as a regulatory protein in cell signaling and transcription. Notably, SOD1 is localized in the nucleus and plays a vital role in oxidative stress response and growth control, especially in the pathogenesis of ALS and cancer.
Article
Cell Biology
Xuetian Yue, Jianming Wang, Chun-Yuan Chang, Juan Liu, Xue Yang, Fan Zhou, Xia Qiu, Vrushank Bhatt, Jessie Yanxiang Guo, Xiaoyang Su, Lanjing Zhang, Zhaohui Feng, Wenwei Hu
Summary: This study found that overexpression of LIF in breast cancer promotes tumorigenesis by increasing glucose uptake and driving glycolysis. It also identifies LIF and its downstream signaling as potential therapeutic targets for breast cancers with LIF overexpression.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Pochung Jordan Chou, Md Shahid Sarwar, Lujing Wang, Renyi Wu, Shanyi Li, Rasika R. Hudlikar, Yujue Wang, Xiaoyang Su, Ah-Ng Kong
Summary: SAHA is able to regulate mitochondrial metabolism, DNA methylome reprogramming, and transcriptomic gene expression, thus inhibiting LPS-induced inflammatory responses in lung epithelial cells. SAHA treatment significantly alters the levels of metabolites involved in methionine, glutathione, and nicotinamide metabolism. Additionally, SAHA revokes differential methylation in certain gene promoter regions and abrogates the expression of proinflammatory cytokine genes.
CANCER PREVENTION RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Yujue Wang, Fredric E. Wondisford, Chi Song, Teng Zhang, Xiaoyang Su