A5017609052- Enzyme Production and Characterization
- Enzyme Structure and Function
- Plant biochemistry and biosynthesis
- Microbial Natural Products and Biosynthesis
- Biofuel production and bioconversion
- Biochemical and Molecular Research
- Enzyme Catalysis and Immobilization
- Microbial Metabolites in Food Biotechnology
- Natural product bioactivities and synthesis
- biodegradable polymer synthesis and properties
- Microbial Metabolic Engineering and Bioproduction
- Microplastics and Plastic Pollution
- Amino Acid Enzymes and Metabolism
- Metal-Catalyzed Oxygenation Mechanisms
- Mycotoxins in Agriculture and Food
- Biochemical and biochemical processes
- Pharmacogenetics and Drug Metabolism
- Carbohydrate Chemistry and Synthesis
- Photosynthetic Processes and Mechanisms
- ATP Synthase and ATPases Research
- Trypanosoma species research and implications
- Polysaccharides and Plant Cell Walls
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Microbial bioremediation and biosurfactants
Hangzhou Normal University
2023-2025
Hubei University
2018-2025
Tianjin Institute of Industrial Biotechnology
2013-2022
Chinese Academy of Sciences
2013-2022
University of Chinese Academy of Sciences
2019-2021
University of Science and Technology of China
2020
Center for Innovation
2019
University of Illinois Urbana-Champaign
2008-2015
John Wiley & Sons (Germany)
2015
Jiangnan University
2014
Abstract PET hydrolase (PETase), which hydrolyzes polyethylene terephthalate (PET) into soluble building blocks, provides an attractive avenue for the bioconversion of plastics. Here we present structures a novel PETase from PET-consuming microbe Ideonella sakaiensis in complex with substrate and product analogs. Through structural analyses, mutagenesis, activity measurements, substrate-binding mode is proposed, several features critical catalysis are elucidated.
We report the discovery of a series new drug leads that have potent activity against Mycobacterium tuberculosis as well other bacteria, fungi, and malaria parasite. The compounds are analogues (TB) SQ109 (1), which has been reported to act by inhibiting transporter called MmpL3, involved in cell wall biosynthesis. show 1 also target enzymes menaquinone biosynthesis electron transport, respiration ATP biosynthesis, uncouplers, collapsing pH gradient membrane potential used power transporters....
Abstract Poly(butylene adipate-co-terephthalate) (PBAT), a polyester made of terephthalic acid (TPA), 1,4-butanediol, and adipic acid, is extensively utilized in plastic production has accumulated globally as environmental waste. Biodegradation an attractive strategy to manage PBAT, but effective PBAT-degrading enzyme required. Here, we demonstrate that cutinases are highly potent enzymes can completely decompose PBAT films 48 h. We further show the engineered cutinases, by applying double...
KRAS mutation occurs in nearly 30% of human cancers, yet the most prevalent and oncogenic KRAS(G12D) variant still lacks inhibitors. Herein, we designed a series potent inhibitors that can form salt bridge with KRAS's Asp12 residue. Our ITC results show these have similar binding affinity both GDP-bound GTP-bound KRAS(G12D), our crystallographic studies reveal structural basis inhibitor binding-induced switch-II pocket experimentally confirming formation between piperazine moiety residue...
Polyethylene terephthalate (PET) is among the most extensively produced plastics, but huge amounts of PET wastes that have accumulated in environment become a serious threat to ecosystem. Applying hydrolytic enzymes depolymerize an attractive measure manage pollution, and searching for more effective prerequisite achieve this goal. A thermostable cutinase originates from leaf-branch compost termed ICCG hydrolase reported so far. Here, we illustrated crystal structure complex with analogue,...
In both cancer and infections, diseased cells are presented to human Vγ9Vδ2 T through an 'inside out' signalling process whereby structurally diverse phosphoantigen (pAg) molecules sensed by the intracellular domain of butyrophilin BTN3A11-4. Here we show how-in humans alpaca-multiple pAgs function as 'molecular glues' promote heteromeric association between domains BTN3A1 similar BTN2A1. X-ray crystallography studies visualized that engagement with forms a composite interface for direct...
Considerable effort has focused on the development of selective protein farnesyl transferase (FTase) and geranylgeranyl (GGTase) inhibitors as cancer chemotherapeutics. Here, we report a new strategy for anticancer therapeutic agents involving inhibition diphosphate synthase (FPPS) (GGPPS), two enzymes upstream FTase GGTase, by lipophilic bisphosphonates. Due to dual site targeting decreased polarity, compounds have activities far greater than do current bisphosphonate drugs in inhibiting...
Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Here, we show that some bisphosphonates can also inhibit geranylgeranyl (GGPPS), as well undecaprenyl (UPPS), a cis-prenyltransferase interest target for antibacterial therapy. Our results on GGPPS (10 structures) there three bisphosphonate-binding sites, consisting FPP or isopentenyl substrate-binding sites...
Many steroids are important pharmaceutically active compounds, while cytochrome P450 monooxygenases (CYPs) attractive enzymes for applications in steroidal drug synthesis. However, the catalytic efficiency of existing P450s is not routinely high enough, as well molecular basis selectivity control unclear, which severely restrict their real applications. Here, a 16β steroid-hydroxylase CYP109B4 from Bacillus sonorensis identified with excellent and activity. The crystallization structural...
Undecaprenyl pyrophosphate synthase (UPPs) catalyzes the consecutive condensation reactions of a farnesyl (FPP) with eight isopentenyl pyrophosphates (IPP), in which new cis-double bonds are formed, to generate undecaprenyl that serves as lipid carrier for peptidoglycan synthesis bacterial cell wall. The structures Escherichia coli UPPs were determined previously an orthorhombic crystal form apoenzyme, complex Mg(2+)/sulfate/Triton, and bound FPP. In further search its catalytic mechanism,...
Toll-like receptor (TLR)-10 remains an orphan without well characterized ligands or functions. Here we reveal that TLR10 is predominantly localized to endosomes and binds dsRNA in vitro at endosomal pH, suggesting a ligand of TLR10. Recognition by activates recruitment myeloid differentiation primary response gene 88 (MyD88) for signal transduction suppression interferon regulatory factor (IRF)-7 dependent type I IFN production. We also demonstrate crosstalk between TLR3, as they compete...
The catalytic domain of XynCDBFV, a glycoside hydrolase family 11 (GH11) xylanase from ruminal fungus Neocallimastix patriciarum previously engineered to exhibit higher specific activity and broader pH adaptability, holds great potential in commercial applications. Here, the crystal structures XynCDBFV its complex with substrate were determined 1.27–1.43 Å resolution. These revealed typical GH11 β-jelly-roll fold detailed interaction networks between enzyme ligands. Notably, an extended...
Trypanosomatid parasites are the causative agents of many neglected tropical diseases and there is currently considerable interest in targeting endogenous sterol biosynthesis these organisms as a route to development novel anti-infective drugs. Here, we report first x-ray crystallographic structures enzyme squalene synthase (SQS) from trypanosomatid parasite, Trypanosoma cruzi, agent Chagas disease. We obtained five T. cruzi SQS eight human with four classes inhibitors: substrate-analog...
We tested the antituberculosis drug SQ109, which is currently in advanced clinical trials for treatment of drug-susceptible and drug-resistant tuberculosis, its vitro activity against trypanosomatid parasite Trypanosoma cruzi, causative agent Chagas disease. SQ109 was found to be a potent inhibitor trypomastigote form parasite, with 50% inhibitory concentration (IC50) cell killing 50 ± 8 nM, but it had little effect (50% effective [EC50], ∼80 μM) red blood hemolysis assay. It also inhibited...
Abstract Cytochrome P450 monooxygenases are versatile heme-thiolate enzymes that catalyze a wide range of reactions. Self-sufficient cytochrome contain the redox partners in single polypeptide chain. Here, we present crystal structure full-length CYP116B46, self-sufficient P450. The continuous chain comprises three functional domains, which align well with direction electrons traveling from FMN to heme through [2Fe-2S] cluster. and cluster positioned closely, facilitates efficient electron...
Imine reductases (IREDs) are increasingly identified and characterized for the reduction of imines reductive amination ketones. However, their practical application is still limited due to low activity poor stability native enzymes. Herein, we developed an engineered IRED through three rounds evolution from wild-type Streptomyces clavuligerus. The specific enzyme, ScIRED-R3-V4, was increased >100-fold, >270-fold. Using more active stable 80 g L–1 cyclic imine 2-(2,5-difluorophenyl)-pyrroline...
Abstract Diterpene synthase VenA is responsible for assembling venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. also demonstrates substrate promiscuity by accepting geranyl pyrophosphate and farnesyl as alternative substrates. Herein, we report the crystal structures of in both apo form holo complex trinuclear magnesium cluster group. Functional structural investigations on atypical 115 DSFVSD 120 motif VenA, versus canonical Asp-rich DDXX(X)D/E,...