Article
Biochemistry & Molecular Biology
Xueqing Du, Xuan Chu, Ning Liu, Xiaoyu Jia, Hui Peng, Yazhong Xiao, Lin Liu, Haizhu Yu, Fudong Li, Chao He
Summary: Members of GT75 family catalyze autoglycosylation and exhibit NDP-pyranose mutase activity. Crystal structures of MtdL in complex with Mn2+ and GDP reveal key residues involved in substrate binding and catalytic reactions. Our results provide insights into the mechanism of NDP-pyranose mutase and highlight the importance of this enzyme family in furanose biosynthesis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Jian Fu, Huixiao Fu, Yufen Xia, Ines N'Go, Jun Cao, Weidong Pan, Stephane P. Vincent
Summary: An in situ screening assay has been developed to discover novel inhibitors of UDP-galactopyranose mutase, a key enzyme in Mycobacterium tuberculosis cell wall biosynthesis. This technology allows for high-throughput synthesis and screening of enzyme inhibitors in a 384-well plate format, leading to the successful identification of UGM ligands and determination of their inhibition levels. This study provides a blueprint for designing enamide structures as new UGM inhibitors and anti-mycobacterial agents.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Dalia M. Ahmed, David A. R. Sanders
Summary: In this study, an integrated biophysical approach was used to investigate the aggregation behavior of MS208 and its analogues against MtUGM, revealing unexpected aggregation behavior.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Chihiro Kadooka, Yutaka Tanaka, Daisuke Hira, Jun-ichi Maruyama, Masatoshi Goto, Takuji Oka
Summary: This study confirms the presence of D-galactofuranose-containing glycans in Aspergillus oryzae and shows that they play an important role in cell wall integrity. Deletion of the ugmA gene affects mycelial elongation and the structure of the cell wall.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Hui Zhou, Yueqiang Xu, Frank Ebel, Cheng Jin
Summary: The study investigated the impact of ugmA, ugmB, and gfsB gene mutations in F. oxysporum f.sp. cucumerinum on its morphogenesis and pathogenicity. Results showed that deletion of the ugmA gene led to various phenotypic abnormalities, including reduced galactofuranose content, slowed growth, impaired conidiation, and loss of pathogenicity in cucumber plantlets.
Article
Chemistry, Medicinal
Dalia M. Ahmed, Jeffrey M. Chen, David A. R. Sanders
Summary: UDP-galactopyranose mutase (UGM) is an essential enzyme involved in bacterial cell wall synthesis. A compound called MS208, which acts as a mixed inhibitor of MtbUGM, has been identified as a potential drug target for developing antituberculosis agents. Further studies were conducted to analyze the structure-activity relationship of MS208 and its analogues, and it was found that while most compounds showed inhibitory activity against MtbUGM, they did not inhibit the growth of Mycobacterium tuberculosis.
Article
Biochemistry & Molecular Biology
Jian Fu, Ziyao He, Huixiao Fu, Yufen Xia, Ines N'Go, Huayong Lou, Jinglan Wu, Weidong Pan, Stephane P. Vincent
Summary: The lack of effective TB treatments due to drug-resistant TB has led to limited drug development activity in this area. This study focuses on the inhibition of the UGM enzyme, which is involved in the biosynthesis of galactan. The synthesized amides derived from rosmarinic acid showed a higher affinity for UGM compared to the corresponding esters. In particular, compound 5h demonstrated interesting binding affinity values. A new UGM SPR assay was also established to confirm the binding of compound 5h to UGM. Overall, this study validates the use of amide bioisosteric strategy for the development of UGM inhibitors from rosmarinic acid.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Shulin Cao, Wenqiang Jiang, Yan Shu, Wei Li, Yani Zhang, Aixiang Zhang, Huaigu Chen
Summary: In this study, the CHY1-interacting protein UGMA was identified and confirmed with yeast two-hybrid assays. Deletion of UGMA led to significant defects in growth, reproduction, cell wall integrity, and pathogenicity in F. graminearum. UGMA is unique to fungi and bacteria and plays an important role as a pathogenic factor, required for cell wall architecture, radial growth, and caspofungin tolerance, making it a promising target for antifungal agent development.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Microbiology
Phuong Tuyen Nguyen, Theresa Wacker, Alistair J. P. Brown, Alessandra da Silva Dantas, Elena Shekhova
Summary: Aspergillus fumigatus is a leading cause of the fungal invasive disease aspergillosis. The increasing prevalence of azole-resistant A. fumigatus isolates highlights the importance of discovering new fungal virulence factors. Nitronate monooxygenases (Nmos) represent potential targets for antifungal compounds. However, Nmos are not essential for the oxidative stress resistance of A. fumigatus in vitro, but they contribute to defense against host immune response and promote fungal virulence.
Article
Multidisciplinary Sciences
Zhu Qiao, Edwin R. Lampugnani, Xin-Fu Yan, Ghazanfar Abbas Khan, Wuan Geok Saw, Patrick Hannah, Feng Qian, Jacob Calabria, Yansong Miao, Gerhard Gruber, Staffan Persson, Yong-Gui Gao
Summary: The study presents crystal structures of the catalytic domain of Arabidopsis CESA3, revealing its role in cellulose synthesis and CESA complex formation. Structural analysis shows that CESA3 can form a homodimer through interactions between specific beta strands. The research provides insights into how UDP-Glc is coordinated in CESAs and how CESAs dimerize to assemble into CSCs in plants.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Chemistry, Multidisciplinary
Marlisa M. Hagemann, Erik D. Hedegard
Summary: Lytic polysaccharide monooxygenases (LPMOs) are copper enzymes that can enhance the breakdown and utilization of recalcitrant polysaccharides such as cellulose. The theoretical investigations on the mechanism of LPMOs provide insights into their catalytic reactions and help answer important questions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Microbiology
Sarah R. Beattie, Damian J. Krysan
Summary: The treatment of invasive mold infections is hindered by the lack of adequate drug options, making drug screening challenging. However, a new high-throughput screening platform and unique assay method have been developed to identify novel mold-active antifungal drugs.
Article
Microbiology
Jose P. Guirao-Abad, Martin Weichert, Gines Luengo-Gil, Sarah Sze Wah Wong, Vishukumar Aimanianda, Christina Grisham, Nikita Malev, Shivani Reddy, Laura Woollett, David S. Askew
Summary: The gene encoding ER-localized P5-type ATPase SpfA in the pathogenic mold Aspergillus fumigatus is a downstream target of the unfolded protein response (UPR) and works together with another ER-localized P-type ATPase, SrcA, to support ER homeostasis, oxidative stress resistance, susceptibility to antifungal drugs, and virulence of A. fumigatus.
Article
Biochemistry & Molecular Biology
Jeremy J. M. Liew, Israa M. El Saudi, Son Nguyen, Denyce K. Wicht, Daniel P. Dowling
Summary: Crystal structures of the Pseudomonas fluorescens MsuD were reported, elucidating its role as an alkanesulfonate monooxygenase and revealing the critical importance of the protein C terminus in stabilizing tetramer formation and the alkanesulfonate-binding site. The study provides a deeper understanding of the functionality of MsuD at the molecular level within the sulfur assimilation pathway.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Koki Makabe, Naoki Ishida, Nanako Kanezaki, Yoshihito Shiono, Takuya Koseki
Summary: The purified recombinant alpha-l-rhamnosidase from Aspergillus oryzae expressed in Pichia pastoris was investigated biochemically and structurally. It showed higher activity towards hesperidin and narirutin compared to neohesperidin and naringin. Kinetic analysis and crystal structure revealed the characteristics and catalytic residues of the enzyme. Asp254 and Glu524 were identified as the catalytic residues and their roles were confirmed by mutational studies.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Sorya Belaz, Thibault Rattier, Pierre Lafite, Philippe Moreau, Francoise H. Routier, Florence Robert-Gangneux, Jean-Pierre Gangneux, Richard Daniellou
CARBOHYDRATE RESEARCH
(2015)
Article
Biochemistry & Molecular Biology
Jakob Engel, Philipp S. Schmalhorst, Anke Tina Krueger, Christina Theda Mueller, Falk F. R. Buettner, Francoise H. Routier
Article
Biochemistry & Molecular Biology
Anke Tina Krueger, Jakob Engel, Falk F. R. Buettner, Francoise H. Routier
Article
Parasitology
Sebastian Damerow, Carolin Hoppe, Giulia Bandini, Patricia Zarnovican, Falk F. R. Buettner, Michael A. J. Ferguson, Francoise H. Routier
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2015)
Article
Infectious Diseases
Sebastian Damerow, Carolin Hoppe, Giulia Bandini, Patricia Zarnovican, Falk R. Buettner, Carsten G. K. Lueder, Michael A. J. Ferguson, Francoise H. Routier
PLOS NEGLECTED TROPICAL DISEASES
(2015)
Article
Microbiology
Joao A. Rodrigues, Alvaro Acosta-Serrano, Markus Aebi, Michael A. J. Ferguson, Francoise H. Routier, Irene Schiller, Simao Soares, Daniel Spencer, Alexander Titz, Iain B. H. Wilson, Luis Izquierdo
Article
Biochemistry & Molecular Biology
Giulia Bandini, Deborah R. Leon, Carolin M. Hoppe, Yue Zhang, Carolina Agop-Nersesian, Melanie J. Shears, Lara K. Mahal, Francoise H. Routier, Catherine E. Costello, John Samuelson
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Ohm Prakash, Jana Fuehring, John Post, Sharon M. Shepherd, Thomas C. Eadsforth, David Gray, Roman Fedorov, Francoise H. Routier
Article
Parasitology
Giulia Bandini, Andreia Albuquerque-Wendt, Jan Hegermann, John Samuelson, Francoise H. Routier
Article
Biochemistry & Molecular Biology
Andreia Albuquerque-Wendt, Hermann J. Huette, Falk F. R. Buettner, Francoise H. Routier, Hans Bakker
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Review
Cell Biology
Danielle J. Lee, Holly O'Donnell, Francoise H. Routier, Joe Tiralongo, Thomas Haselhorst
Article
Biochemistry & Molecular Biology
Andreia Albuquerque-Wendt, Damien Jacot, Nicolas Dos Santos Pacheco, Carla Seegers, Patricia Zarnovican, Falk F. R. Buettner, Hans Bakker, Dominique Soldati-Favre, Francoise H. Routier
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Immunology
Alibek Galeev, Abdulhadi Suwandi, Hans Bakker, Ade Oktiviyari, Francoise H. Routier, Lena Krone, Michael Hensel, Guntram A. Grassl
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Carla I. I. Seegers, Isabel Ramon Roth, Patricia Zarnovican, Falk F. R. Buettner, Francoise H. Routier
Summary: This study describes a gene cluster in the human pathogenic fungus Aspergillus fumigatus that is involved in the synthesis of the glycosphingolipid Af3c. The function of the genes in this cluster was determined by analyzing glycolipids extracted from A. fumigatus strains deficient in one of the genes. The reconstitution of the Af3c biosynthetic pathway in yeast confirmed the roles of the genes. The absence of Af3c slightly reduced the virulence of A. fumigatus in a Galleria mellonella infection model.
Article
Biochemistry & Molecular Biology
Carolin M. Hoppe, Andreia Albuquerque-Wendt, Giulia Bandini, Deborah R. Leon, Aleksandra Shcherbakova, Falk F. R. Buettner, Luis Izquierdo, Catherine E. Costello, Hans Bakker, Francoise H. Routier