A5025316927- RNA and protein synthesis mechanisms
- Heat shock proteins research
- Poxvirus research and outbreaks
- DNA and Nucleic Acid Chemistry
- Bacteriophages and microbial interactions
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Virus-based gene therapy research
- NF-κB Signaling Pathways
- Enzyme Structure and Function
- Trypanosoma species research and implications
- Protein Structure and Dynamics
- Inflammasome and immune disorders
- Invertebrate Immune Response Mechanisms
- RNA regulation and disease
- ATP Synthase and ATPases Research
- RNA Research and Splicing
- Viral Infections and Immunology Research
- Parkinson's Disease Mechanisms and Treatments
- Biochemical and Molecular Research
- Mitochondrial Function and Pathology
- Herpesvirus Infections and Treatments
- Psoriasis: Treatment and Pathogenesis
- thermodynamics and calorimetric analyses
Suzhou Municipal Hospital
2024-2025
Nanjing Medical University
2025
Soochow University
2024
First Affiliated Hospital of Soochow University
2024
Oklahoma State University
2014-2023
The University of Texas Health Science Center at San Antonio
2018
Oklahoma State University Oklahoma City
2011-2016
University of Washington
2003-2010
Ruijin Hospital
2009
Noble
2008-2009
Mutations in leucine-rich repeat kinase 2 ( LRRK2 ) are the most common cause of Parkinson's disease (PD). contains a Ras complex proteins (ROC) domain that may act as GTPase to regulate its protein activity. The structure ROC and mechanism(s) by which it regulates activity not known. Here, we report crystal with GDP-Mg 2+ at 2.0-Å resolution. displays dimeric fold generated extensive domain-swapping, resulting pair active sites constructed essential functional groups contributed from both...
Arthropod phenoloxidase (PO) generates quinones and other toxic compounds to sequester kill pathogens during innate immune responses. It is also involved in wound healing physiological processes. Insect PO activated from its inactive precursor, prophenoloxidase (PPO), by specific proteolysis via a serine protease cascade. Here, we report the crystal structure of PPO lepidopteran insect at resolution 1.97 A, which initial for type 3 copper protein family. Manduca sexta heterodimer consisting...
Abstract The 90 kDa heat shock protein (Hsp90) is a molecular chaperone responsible for folding proteins that are directly associated with cancer progression. Consequently, inhibition of the Hsp90 machinery results in combinatorial attack on numerous oncogenic pathways. Seventeen small-molecule inhibitors have entered clinical trials, all which bind N-terminus and exhibit pan-inhibitory activity against four isoforms. pan-Inhibition appears to be detrimental as toxicities been reported...
The 90 kDa heat shock protein (Hsp90) is a molecular chaperone that processes nascent polypeptides into their biologically active conformations. Many of these proteins contribute to the progression cancer, and consequently, inhibition Hsp90 folding machinery represents an innovative approach toward cancer chemotherapy. However, clinical trials with N-terminal inhibitors have encountered deleterious side effects toxicities, which appear result from pan-inhibition all four isoforms. Therefore,...
Four-stranded guanine tetraplexes in RNA have been identified to be involved crucial biological functions, such as dimerization of retroviral RNA, translational repression, and mRNA turnover. However, the structural basis for these processes is still largely unknown. Here we report tetraplex structure (UGGGGU) 4 at ultra-high resolution (0.61 Å). The space group P 42 1 2, cell constants are a = b 36.16 Å c 74.09 Å. was solved by multiple-wavelength anomalous dispersion method using set...
As a defense strategy against viruses or competitors, some microbes use anticodon nucleases (ACNases) to deplete essential tRNAs, effectively halting global protein synthesis. However, this mechanism has not been observed in multicellular eukaryotes. Here, we report that human SAMD9 is an ACNase specifically cleaves phenylalanine tRNA (tRNA
Human interleukin-18 (hIL-18) is a cytokine that plays an important role in inflammation and host defense against microbes. Its activity regulated vivo by naturally occurring antagonist, the human IL-18-binding protein (IL-18BP). Functional homologs of IL-18BP are encoded all orthopoxviruses, including variola virus, causative agent smallpox. They contribute to virulence suppressing IL-18-mediated immune responses. Here, we describe 2.0-A resolution crystal structure orthopoxvirus IL-18BP,...
Significance SAMD9 and SAMD9L (SAMD9/9L) are important innate immune defenders against viruses the development of myeloid tumors. They form a crucial host barrier that poxviruses must overcome for successful infection. A myriad human diseases including many pediatric myelodysplastic syndromes caused by mutations in SAMD9/9L. However, molecular functions SAMD9/9L how their executed unknown, hindering progress developing effective therapies SAMD9/9L-associated diseases. Here, we identified...
Background Previous studies have highlighted the effects of diet and gut microbiota on incidence kidney stones, dietary index for (DI-GM) is a new that accurately represents variety microbiota. The current study intends to examine potential correlation between DI-GM stones. Methods Data from 2007–2018 National Health Nutrition Examination Survey (NHANES) were employed in this cross-sectional study. history stones was assessed using conditions questionnaire. In order multivariate logistic...
Freezing of purified protein drops directly in liquid nitrogen is a convenient technique for the long-term storage samples. Although this enhances reproducibility follow-up crystallization experiments, some samples are not amenable to technique. It has been discovered that plunging PCR tubes containing into results more rapid freezing and can safely preserve proteins damaged by drop-freezing. The PCR-tube method also be adapted PCR-plate with applications high-throughput structural genomics projects.
A cell-permeable peptide derived from an adaptor protein blocks cytokine receptor signaling and reduces inflammation.
Phenoloxidase (PO)-catalyzed melanization is a universal defense mechanism of insects against pathogenic and parasitic infections. In mosquitos such as Anopheles gambiae, melanotic encapsulation resistance certain parasites that cause malaria filariasis. PO initially synthesized by hemocytes released into hemolymph inactive prophenoloxidase (PPO), which activated serine protease cascade upon recognition foreign invaders. The mechanisms PPO activation catalysis have been elusive. Herein, we...
The 20S editosome, a multiprotein complex, catalyzes the editing of most mitochondrial mRNAs in trypanosomatids by uridylate insertion and deletion. RNAi mediated inactivation expression KREPA4 (previously TbMP24), component procyclic form Trypanosoma brucei resulted inhibition cell growth, loss RNA editing, disappearance editosomes. Levels MRP1 REAP-1 proteins, which may have roles but are not editosome components, were unaffected. Tagged protein is incorporated into editosomes vivo with no...
Mitochondrial mRNA editing in trypanosomatid parasites involves several multiprotein assemblies, including three very similar complexes that contain the key enzymatic activities and sediment at ~20S on glycerol gradients. These editosomes have a common set of 12 proteins, enzymes for uridylyl (U) removal addition, 2 RNA ligases, proteins with RNase III-like domains, 6 predicted oligonucleotide binding (OB) folds. In each 3 distinct contains different III-type endonuclease, 1 related and, one...
A series of novel anthracene L-rhamnopyranosides compounds were designed and synthesized their anti-proliferative activities on cancer cell lines investigated. We found that one derivative S-8 (EM-d-Rha) strongly inhibited proliferation a panel different human including A549, HepG2, OVCAR-3, HeLa K562 SGC-790 lines, displayed IC50 values in low micro-molar ranges, which are ten folds more effective than emodin. In addition, we EM-d-Rha...
During our efforts to characterize the regulatory properties of human liver pyruvate kinase (L-PYK), we have noted that affinity protein for phosphoenolpyruvate (PEP) becomes reduced several days after cell lysis. A 1.8 Å crystallographic structure L-PYK with S12D mimic phosphorylation indicates Cys436 is oxidized, first potential insight into explaining effect "aging". Interestingly, oxidation only sulfenic acid despite crystal growth time period 2 weeks. Mutagenesis confirms side chain...
IL-17 cytokines play a crucial role in variety of inflammatory and autoimmune diseases. They signal through heterodimeric receptor complexes consisting members IL-17R family. A unique intracellular signaling domain was identified within all IL-17Rs, termed similar expression to fibroblast growth factor genes (SEFIR). SEFIR is also found NF-κB activator 1 (Act1), an E3 ubiquitin ligase, mediates its recruitment IL-17Rs. In this study, our knowledge, we report the structure first from IL-17RB...