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
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
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
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
Microbiology
Yunyun Wei, Dan He, Busi Zhao, Yuhuan Liu, Song Gao, Xiaowei Zhang, Li Wang
Summary: In this study, the sat1 gene in Aspergillus fumigatus was characterized, and its important role in growth and virulence was demonstrated, likely through its effects on cell wall synthesis and mitochondrial functions.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Marketa Samalova, Patricia Flamant, Remi Beau, Mike Bromley, Maryse Moya-Nilges, Thierry Fontaine, Jean-Paul Latge, Isabelle Mouyna
Summary: An analysis of the Aspergillus fumigatus genome has identified 86 genes coding for GPI-APs. These proteins have diverse functions in cell wall remodeling, virulence, and adhesion. The study focused on a new GPI-anchored protein called SwgA, which is found in the Clavati of Aspergillus and is involved in germination, growth, and morphogenesis, as well as nitrogen metabolism and thermosensitivity. The findings suggest that GPI-APs have broader roles in fungal metabolism beyond cell wall biosynthesis.
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
Katherine Gonzalez, Gauri Gangapurwala, Julien Alex, Antje Vollrath, Zoltan Cseresnyes, Christine Weber, Justyna A. Czaplewska, Stephanie Hoeppener, Carl-Magnus Svensson, Thomas Orasch, Thorsten Heinekamp, Carlos Guerrero-Sanchez, Marc Thilo Figge, Ulrich S. Schubert, Axel A. Brakhage
Summary: The study investigated whether polymeric particles (PPs) can reach Aspergillus fumigatus conidia-containing phagolysosomes in macrophages. The results showed that PPs were efficiently taken up by macrophages and co-localized with conidia in the same phagolysosomes. Fusion of phagolysosomes containing PPs with phagolysosomes containing conidia was observed. This suggests that PPs can be used as a carrier system to target intracellular pathogens.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Immunology
Huijuan Song, Siyu Zou, Yi Huang, Yun Wang, Ting Wang, Wei Wei, Ziyong Sun, Hongyan Hou
Summary: This study retrospectively analyzed the pathogenic and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) patients with co-infections. The findings revealed a higher mortality rate among SFTS patients with co-infection compared to those without co-infection. The pathogens responsible for co-infection were primarily isolated from respiratory specimens, with fungal and bacterial infections being the most common. SFTS patients with co-infection displayed significant alterations in inflammatory markers, coagulation function, and liver function indicators compared to non-co-infection patients.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Chemistry, Applied
Hao Ding, Jia-Peng Wang, Si-Ping Deng, Jun-Li Gan, Bing-Xian Li, Ling-Ling Yao, Sheng-Qi Zhang, Le Cai, Zhong-Tao Ding
Summary: A new bergamotane sesquiterpenoid, fumigatanol, along with nine known compounds were isolated from Aconitum-derived fungus Aspergillus fumigatus M1. The structures of these compounds were determined through extensive spectroscopic analyses, ECD experiment, and NMR computational method. The antibacterial and cytotoxic activities of the new compound were evaluated and found to be negligible.
NATURAL PRODUCT RESEARCH
(2023)
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
Chemistry, Medicinal
Rui Zhang, Haifeng Wang, Baosong Chen, Huanqin Dai, Jingzu Sun, Junjie Han, Hongwei Liu
Summary: In this study, six new compounds and thirty-nine known ones were isolated from the marine-derived fungus Aspergillus fumigatus H22. Nearly half of the compounds exhibited antibacterial activity, especially compounds 8 and 11, and 33-38 showed excellent antimicrobial activities against MRSA.
Article
Agronomy
Junfeng Tan, Junwei Yang, Nuerbiye Aobulikasimu, Chen Zhang, Bixuan Cao, Hang Lv, Mingguo Jiang, Li Han, Xueshi Huang
Summary: This study investigated the antifungal activities of natural and artificial phthalides and explored their structure-activity relationships. The benzene ring moiety played an essential role in their antifungal activities, and oxygen-containing substituents on the benzene ring significantly impacted their activities, with free hydroxyl being favorable. Senkyunolide B (SENB), a typical phthalide, exhibited broad antifungal activities against human and plant pathogenic fungi, especially Aspergillus fumigatus. SENB affected the spore germination and hyphae growth of Aspergillus fumigatus by down-regulating the phosphatidylinositol-PKC-calcineurin axis and ENG gene expression. Moreover, SENB disrupted the oxidation-reduction process in Aspergillus fumigatus, destroying mature biofilms. In vivo experiments showed that SENB significantly prolonged survival and reduced fungal burden in a mouse model of invasive pulmonary aspergillosis.
PEST MANAGEMENT SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
David A. Korasick, John J. Tanner
Summary: Certain mutations in the ALDH7A1 gene cause pyridoxine-dependent epilepsy (PDE), characterized by seizures and sometimes intellectual disability. These mutations, including over 70 missense mutations, have complex effects on the structure and catalytic activity of ALDH7A1. Mutations targeting active site residues and those remote from the site show varied impact, indicating the challenge in predicting the effects of missense mutations on enzyme function. Additional biophysical analyses of disease-causing mutations are necessary to develop predictive rules for enzyme structure and function.
Article
Biochemistry & Molecular Biology
Hao Li, Benedicta Forson, Meital Eckshtain-Levi, Hannah Valentino, Julia S. Martin del Campo, John J. Tanner, Pablo Sobrado
Summary: The study investigated the enzyme-enzyme interactions, catalytic reaction kinetics, and FAD binding properties of FRED and IBAH in the FRED:IBAH system. Results showed the formation of a protein-protein complex for direct transfer of reduced flavin from the reductase to the monooxygenase in this two-component system.
Article
Biochemistry & Molecular Biology
Ashley C. Campbell, Alexandra N. Bogner, Yizi Mao, Donald F. Becker, John J. Tanner
Summary: The study investigates the inhibition of PutA protein by proline stereoisomers and analogs through high-resolution crystal structures; the compounds are weak inhibitors with millimolar inhibition constants. The structural and kinetic data expand understanding of the interaction between proline-like molecules and GSALDH, providing insight into the relationship between stereochemistry and inhibitor affinity.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Virology
Ashley C. Campbell, John J. Tanner, Kurt L. Krause
Summary: This study presents a method for producing neuraminidase from a human cell line, which yielded high levels of soluble expression and supported high resolution crystal structure determination. The method is expected to be useful in further studies, such as the characterization of inhibitor binding.
Article
Chemistry, Multidisciplinary
Hannah Valentino, David A. Korasick, Tabbetha J. Bohac, Justin A. Shapiro, Timothy A. Wencewicz, John J. Tanner, Pablo Sobrado
Summary: Acinetobacter baumannii is an opportunistic pathogen with a high mortality rate, and the synthesis and uptake of iron-chelating siderophores Acinetobactin (Acb) and preacinetobactin (pre-Acb) are crucial for its virulence. The flavin-dependent siderophore-interacting protein (SIP) BauF plays a key role in the reduction of Fe(III) bound to Acb/pre-Acb and the release of Fe(II), with NAD(P)H not being its physiological partners. The structural and biochemical data presented validate the importance of BauF in A. baumannii iron assimilation, providing valuable information for drug design.
Article
Biochemistry & Molecular Biology
Sagar M. Patel, Javier Seravalli, Kyle M. Stiers, John J. Tanner, Donald F. Becker
Summary: L-Thioproline is a cyclic sulfur-containing analog of l-proline found in various organisms, and human PYCR isozymes 1 and 2 show significant dehydrogenase activity towards L-T4C. This suggests a new enzyme function for PYCRs in the metabolism of L-T4C, leading to cysteine formation.
Article
Biochemistry & Molecular Biology
David A. Korasick, Shelbi L. Christgen, Insaf A. Qureshi, Donald F. Becker, John J. Tanner
Summary: This study investigated the mechanism of proline utilization enzyme in bacteria using tunnel-blocking mutagenesis, revealing that Trp206 plays a crucial role in inhibiting the auxiliary tunnel 2a and impairing PRODH activity. Further experiments indicated that Trp206 may affect the binding of L-proline substrate and the closure of the PRODH active site by disrupting a specific ion pair.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Yizi Mao, Javier Seravalli, Thomas G. Smith, Martha Morton, John J. Tanner, Donald F. Becker
Summary: Thiazolidine carboxylates T4C and T2C, sulfur analogues of proline, are substrates for the enzyme PutA, which catalyzes their oxidation. The oxidation of T4C leads to cysteine formation, while oxidation of T2C generates a stable Delta(4)-thiazoline-2-carboxylate species.
Article
Chemistry, Organic
Alexandra N. Bogner, John J. Tanner
Summary: In this study, the inhibition of PRODH by 18 proline-like compounds was investigated to understand the structural and chemical features responsible for the affinity of the best-known inhibitor. The results revealed new structure-affinity relationships that could be utilized in the development of new inhibitor design strategies targeting PRODH.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Noah S. Lyons, John J. Tanner, Alexandra N. Bogner, Pablo Sobrado
Summary: Acinetobacter baumannii is a Gram-negative opportunistic pathogen that causes nosocomial infections. The rise of multidrug resistant strains of A. baumannii has limited the use of standard antibiotics, highlighting a need for new drugs that exploit novel mechanisms of pathogenicity. This study investigated FbsI, an N-hydroxylating monooxygenase involved in the biosynthesis of the major siderophore produced by A. baumannii. The results provide insights into the substrate recognition and catalytic cycle of FbsI, and have implications for understanding the pathogenic mechanisms and developing new antibiotics.
Article
Biochemistry & Molecular Biology
Kaylen R. Meeks, John J. Tanner
Summary: PYCRs are important enzymes involved in the biosynthesis of proline. They have been extensively studied in cancer, especially PYCR1, due to their role in altered metabolism. This study presents a method for expressing and purifying PYCR3 in E. coli. It shows that the activity of PYCR3 is dependent on the type of coenzyme used. Competitive inhibition assays were performed with proline analogs, and a higher selectivity for PYCR1 than PYCR3 was observed with N-formyl-L-proline.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
David A. Korasick, Luckio F. Owuocha, Pramod K. Kandoth, John J. Tanner, Melissa G. Mitchum, Lesa J. Beamer
Summary: This study investigates the effects of single variants P130R and N358Y in soybean SHMT8. The results demonstrate that these two variants have reduced catalytic activity compared to the susceptible Essex SHMT8, but are more active than the P130R/N368Y double variant. Additionally, the single variants lack THF-substrate inhibition, unlike Essex SHMT8. The crystal structures of the variants provide insights into the structural impacts of the mutations and allosteric regulation.
Article
Multidisciplinary Sciences
Cole E. E. McKay, Jianlin Cheng, John J. J. Tanner
Summary: The crystal structure of the domain of unknown function family 507 protein from Aquifex aeolicus was determined, revealing a Y-shaped α-helical structure with pseudo-twofold symmetry. The structures differ in their C-terminal arm rotation, suggesting a potential functional site.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
David P. Buckley, Marie E. Migaud, John J. Tanner
Summary: ox-NADs are redox inactive derivatives of NAD that accumulate in cells under stress and may act as potential inhibitors of enzymes. Molecular dynamics simulations reveal distinct conformational preferences of ox-NADs in solution, which could aid in identifying enzymes targeted by ox-NADs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alexandra N. Bogner, Juan Ji, John J. Tanner
Summary: In this study, minimal PRODH domains have been engineered for inhibitor discovery, with designs containing approximately one-third of the PutA amino acid sequence and replacing a domain of PutA. The minimal PRODHs exhibit near wild-type enzymatic activity and are susceptible to known inhibitors and inactivators. Crystal structures of minimal PRODHs inhibited by specific compounds were determined, showing potential usefulness in chemical probe discovery.
PROTEIN ENGINEERING DESIGN & SELECTION
(2022)