Review
Chemistry, Multidisciplinary
Jacque L. Faylo, Trey A. Ronnebaum, David W. Christianson
Summary: The chemodiversity of terpenoid natural products is largely attributed to the catalysis of prenyltransferases and cyclases, which generate complex hydrocarbon compounds through chain elongation reactions. Terpene cyclization reactions are characterized by changes in chemical bonding of substrate carbon atoms, with different classes of cyclases based on the chemistry of carbocation formation.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Jialiang Wang, Xiaojie Wang, Xixi Li, LiangLiang Kong, Zeqian Du, Dandan Li, Lixia Gou, Hao Wu, Wei Cao, Xiaozheng Wang, Shuangjun Lin, Ting Shi, Zixin Deng, Zhijun Wang, Jingdan Liang
Summary: This study presents the cryo-EM structure of CalA3, a chain release PKS module without an ACP domain, and its structures with amidation or hydrolysis products. The unique infinity-shaped dimeric architecture of CalA3 with five connected domains is revealed. The cryo-EM structures of the ketosynthase (KS) domain of CalA3 provide insights into its mechanism for mediating C-N bond formation.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Johannes Haeberle, Marvin B. Moore, Nantaporn Haskins, Veronique Rufenacht, Dariusz Rokicki, Estela Rubio-Gozalbo, Mendel Tuchman, Nicola Longo, Mark Yandell, Ashley Andrews, Nicholas AhMew, Ljubica Caldovic
Summary: N-acetylglutamate synthase deficiency is an autosomal recessive urea cycle disorder that can be effectively treated with N-carbamylglutamate. Research suggests that analyzing noncoding regions of NAGS and other urea cycle genes could reveal molecular causes of disease and identify novel regulators of ureagenesis.
Article
Chemistry, Multidisciplinary
Paramita Pal, Serena M. L. Wessely, Craig A. Townsend
Summary: Naturally occurring enediynes have complex structures and potent DNA cleaving ability, making them useful in cancer chemotherapy. Dynemicin A is an exceptional member of anthraquinone-fused enediynes, derived from the same biosynthetic building block. Deletions of two biosynthetic protein genes, DynO6 and DynA5, affect the synthesis of Dynemicin A, but the Delta dynA5 strain still retains some ability to produce it. The appearance of unexpected structures and contradictory experimental data contribute to the understanding of the downstream steps in Dynemicin A biosynthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Margarita A. Tararina, Danielle A. Yee, Yi Tang, David W. Christianson
Summary: The fungal species Aspergillus flavus produces flavunoidine, an alkaloid terpenoid, through a unique biosynthetic pathway. The enzyme FlvF plays a key role in this pathway by forming specific C-N bonds. The crystal structure of FlvF was determined and it was found to have a similar fold to class I terpene synthases, although it lacks their enzymatic activity. The binding of two ligands in the active site of FlvF provided insights into the docking of the substrate and the generation of a model of the enzyme-product complex. Phylogenetic analysis of FlvF and related enzymes suggests the possibility of different substrates being linked to a common core to produce flavunoidine congeners.
Article
Chemistry, Medicinal
Thanapon Charoenwongpaiboon, Methus Klaewkla, Pimchai Chaiyen, Chanakan Tongsook
Summary: 8-Demethyl-8-dimethylaminoriboflavin (RoF) is a natural riboflavin analogue with potent antibiotic properties. Catalyzed by N,N-8-Demethyl-8-aminoriboflavin dimethyltransferase (RosA), RoF is synthesized through a consecutive dimethylation reaction of 8-demethyl-8-aminoriboflavin (AF). Molecular dynamics simulations revealed mechanistic insights into RoF synthesis by RosA, suggesting the role of substrate positioning and ligand binding in the reaction.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Agriculture, Multidisciplinary
Woojin Park, Hyeoncheol Francis Son, Donghoon Lee, Il-Kwon Kim, Kyung-Jin Kim
Summary: In this study, the crystal structure of TrpCF from Corynebacterium glutamicum was identified and the active site was elucidated using rCdRP. Through site-directed mutagenesis experiments, a variant with enhanced activity, CgTrpCF(P294K) (PRAI(CD/P294K)), was obtained.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Nina Urbeliene, Matas Tiskus, Giedre Tamulaitiene, Renata Gasparaviciute, Ringaile Lapinskaite, Vykintas Jauniskis, Jurgis Sudzius, Rita Meskiene, Daiva Tauraite, Emilija Skrodenyte, Gintaras Urbelis, Justas Vaitekunas, Rolandas Meskys
Summary: Prokaryotic homo-tetrameric CDAs were found to catalyze nucleophilic substitutions, producing uridine and corresponding amide, amine, carbamate, thiol, or alcohol as leaving groups. The volume of the binding pocket of CDAs is related to the bulkiness of the leaving group, which is determined by the flexible beta 3 alpha 3 loop of CDAs. CDAs with broad substrate activity participate in the salvage and/or catabolism of variously modified pyrimidine nucleosides, expanding our knowledge of cellular turnover and pharmacokinetics.
Article
Biochemistry & Molecular Biology
Tomohiro Suzuki, Takeo Tomita, Kenta Hirayama, Michio Suzuki, Tomohisa Kuzuyama, Makoto Nishiyama
Summary: The crystal structure of a truncated form of homocitrate synthase lacking the RAM domain has been determined, revealing the involvement of subdomain II in acetyl-CoA recognition. This provides important clues for a better understanding of the catalytic mechanism of HCS within the enzyme family.
Article
Biochemistry & Molecular Biology
Trey A. Ronnebaum, Samuel A. Eaton, Emily A. E. Brackhahn, David W. Christianson
Summary: The study explores the structure-function relationships of the prenyltransferase alpha domain in the bifunctional diterpene synthase from Penicillium verruculosum, aiming to generate alternative linear isoprenoid products. Site-specific variants at certain positions can alter product types, while mutations in the catalytic general acid of the class II cyclase domain significantly compromise prenyltransferase activity.
Article
Multidisciplinary Sciences
Diego F. Gauto, Pavel Macek, Duccio Malinverni, Hugo Fraga, Matteo Paloni, Iva Sucec, Audrey Hessel, Juan Pablo Bustamante, Alessandro Barducci, Paul Schanda
Summary: This study reveals the critical role of a flexible loop in the function of an aminopeptidase and demonstrates the ability of magic-angle spinning NMR to provide atomic-level quantitative insights in a very large complex.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Alex H. Y. Chan, Terence C. S. Ho, Rimsha Irfan, Rawia A. A. Hamid, Emma S. Rudge, Amjid Iqbal, Alex Turner, Anna K. H. Hirsch, Finian J. Leeper
Summary: Thiamine diphosphate (ThDP), the bioactive form of vitamin B1, is crucial for cellular metabolism. ThDP-dependent enzymes rely on ThDP as a coenzyme for catalytic activity, but differ in substrate preferences. Thiamine/ThDP analogues have been used to study these enzymes, but questions about ligand design strategy and selectivity remain. This study compares derivatives of these analogues with different aromatic rings as inhibitors, and explores the impact of introducing a C2-substituent.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Daniel E. Felton, Tsuyoshi A. Kohlgruber, Zachary D. Tucker, Eva M. Gulotty, Brandon L. Ashfeld, Peter C. Burns
Summary: In this study, ionothermal syntheses were used to control the formation of uranyl salt complexes. The high thermal stability and ligation potential of ionic liquids were utilized to enable the ligation of the anionic component and promote speciation. The study also investigated the factors influencing the formation of uranyl complexes, such as the type of cation in the ionic liquid and the choice of uranium source.
CRYSTAL GROWTH & DESIGN
(2023)
Article
Biotechnology & Applied Microbiology
Yuru Tong, Xiaoli Ma, Tianyuan Hu, Kang Chen, Guanghong Cui, Ping Su, Haifeng Xu, Wei Gao, Tao Jiang, Luqi Huang
Summary: In this study, the intermediate of Selaginella moellendorffii miltiradiene synthase (SmMDS) synthesis was confirmed through mutagenesis studies. The contribution of key residues in active sites and the transport of intermediates between different active sites were analyzed. The research provides new insights into the mechanism and regulation of diterpene synthesis.
PLANT BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Ju Hyeong Kim, Gwan Hee Lee, Jae-Hee Jeong, Yeon-Gil Kim, Hyun Ho Park
Summary: Protein quality control mechanisms are crucial for cellular integrity, and the HtrA family of serine proteases plays a key role in folding stress in the prokaryotic periplasm. This study presents the structure of MucD from Pseudomonas syringae, revealing its similarities and differences with other HtrA family members. The study also provides a model of psMucD's catalytic process.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Dashuang Shi, Norma M. Allewell, Mendel Tuchman
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2015)
Review
Biochemistry & Molecular Biology
Dashuang Shi, Norma M. Allewell, Mendel Tuchman
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2015)
Article
Parasitology
Yongdong Li, Pan Li, Yun Peng, Qunfeng Wu, Fuyan Huang, Xiang Liu, Xun Li, Hui Zhou, Daoyi Guo, Dashuang Shi, Xiao-Nong Zhou, Xiaolin Fan
Article
Biochemical Research Methods
Gengxiang Zhao, Zhongmin Jin, Norma M. Allewell, Mendel Tuchman, Dashuang Shi
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2015)
Article
Endocrinology & Metabolism
Dashuang Shi, Gengxiang Zhao, Nicholas Ah Mew, Mendel Tuchman
MOLECULAR GENETICS AND METABOLISM
(2017)
Article
Biochemistry & Molecular Biology
Gengxiang Zhao, Norma M. Allewell, Mendel Tuchman, Dashuang Shi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2013)
Article
Biochemistry & Molecular Biology
Gengxiang Zhao, Nantaporn Haskins, Zhongmin Jin, Norma M. Allewell, Mendel Tuchman, Dashuang Shi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2013)
Article
Chemistry, Organic
An Xiao, Teri J. Slack, Yanhong Li, Dashuang Shi, Hai Yu, Wanqing Li, Yang Liu, Xi Chen
JOURNAL OF ORGANIC CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Jianhua Wei, Yang Xue, Lian Wu, Jie Ma, Xiuli Yi, Junrui Zhang, Bin Lu, Chunying Li, Dashuang Shi, Songtao Shi, Xinghua Feng, Tao Cai
Article
Multidisciplinary Sciences
Gengxiang Zhao, Zhongmin Jin, Norma M. Allewell, Mendel Tuchman, Dashuang Shi
Article
Biochemistry & Molecular Biology
Gengxiang Zhao, Zhongmin Jin, Yanli Wang, Norma M. Allewell, Mendel Tuchman, Dashuang Shi
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2013)
Article
Biochemical Research Methods
David Jimenez-Morales, Larisa Adamian, Dashuang Shi, Jie Liang
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2014)
Article
Biochemical Research Methods
Yongdong Li, Qunfeng Wu, Yun Peng, Fuyan Huang, Xun Li, Lin Chen, Dashuang Shi, Xiaonong Zhou, Xiaolin Fan
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2014)
Article
Biochemistry & Molecular Biology
Teri J. Slack, Wanqing Li, Dashuang Shi, John B. McArthur, Gengxiang Zhao, Yanhong Li, An Xiao, Zahra Khedri, Hai Yu, Yang Liu, Xi Chen
BIOORGANIC & MEDICINAL CHEMISTRY
(2018)
Review
Biology
Dashuang Shi, Ljubica Caldovic, Mendel Tuchman