Sulfonylurea resistance reconstitution as a novel strategy for ILV2-specific integration in Magnaporthe oryzae

2014 ◽  
Vol 68 ◽  
pp. 71-76 ◽  
Author(s):  
Fan Yang ◽  
Naweed I. Naqvi
Keyword(s):  
Magnaporthe Oryzae ◽  
Novel Strategy

Crystal structures of Magnaporthe oryzae trehalose-6-phosphate synthase (MoTps1) suggest a model for catalytic process of Tps1

2019 ◽  
Vol 476 (21) ◽  
pp. 3227-3240 ◽  
Author(s):  
Shanshan Wang ◽  
Yanxiang Zhao ◽  
Long Yi ◽  
Minghe Shen ◽  
Chao Wang ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Conformational Changes ◽  
Magnaporthe Oryzae ◽  
Structural Information ◽  
Complex Structure ◽  
Critical Role ◽  
Catalytic Process ◽  
Structural Basis ◽  
Salt Bridges ◽  
Terminal Domain

Trehalose-6-phosphate (T6P) synthase (Tps1) catalyzes the formation of T6P from UDP-glucose (UDPG) (or GDPG, etc.) and glucose-6-phosphate (G6P), and structural basis of this process has not been well studied. MoTps1 (Magnaporthe oryzae Tps1) plays a critical role in carbon and nitrogen metabolism, but its structural information is unknown. Here we present the crystal structures of MoTps1 apo, binary (with UDPG) and ternary (with UDPG/G6P or UDP/T6P) complexes. MoTps1 consists of two modified Rossmann-fold domains and a catalytic center in-between. Unlike Escherichia coli OtsA (EcOtsA, the Tps1 of E. coli), MoTps1 exists as a mixture of monomer, dimer, and oligomer in solution. Inter-chain salt bridges, which are not fully conserved in EcOtsA, play primary roles in MoTps1 oligomerization. Binding of UDPG by MoTps1 C-terminal domain modifies the substrate pocket of MoTps1. In the MoTps1 ternary complex structure, UDP and T6P, the products of UDPG and G6P, are detected, and substantial conformational rearrangements of N-terminal domain, including structural reshuffling (β3–β4 loop to α0 helix) and movement of a ‘shift region' towards the catalytic centre, are observed. These conformational changes render MoTps1 to a ‘closed' state compared with its ‘open' state in apo or UDPG complex structures. By solving the EcOtsA apo structure, we confirmed that similar ligand binding induced conformational changes also exist in EcOtsA, although no structural reshuffling involved. Based on our research and previous studies, we present a model for the catalytic process of Tps1. Our research provides novel information on MoTps1, Tps1 family, and structure-based antifungal drug design.

The Collaborative Network Approach: a model for advancing patient-centric research for Castleman disease and other rare diseases

2019 ◽  
Vol 3 (1) ◽  
pp. 97-105
Author(s):  
Mary Zuccato ◽  
Dustin Shilling ◽  
David C. Fajgenbaum
Keyword(s):  
Rare Diseases ◽  
Treatment Options ◽  
Castleman Disease ◽  
High Impact ◽  
Collaborative Network ◽  
Network Approach ◽  
Grant Applications ◽  
Research Questions ◽  
Novel Strategy ◽  
Patient Centric

Abstract There are ∼7000 rare diseases affecting 30 000 000 individuals in the U.S.A. 95% of these rare diseases do not have a single Food and Drug Administration-approved therapy. Relatively, limited progress has been made to develop new or repurpose existing therapies for these disorders, in part because traditional funding models are not as effective when applied to rare diseases. Due to the suboptimal research infrastructure and treatment options for Castleman disease, the Castleman Disease Collaborative Network (CDCN), founded in 2012, spearheaded a novel strategy for advancing biomedical research, the ‘Collaborative Network Approach’. At its heart, the Collaborative Network Approach leverages and integrates the entire community of stakeholders — patients, physicians and researchers — to identify and prioritize high-impact research questions. It then recruits the most qualified researchers to conduct these studies. In parallel, patients are empowered to fight back by supporting research through fundraising and providing their biospecimens and clinical data. This approach democratizes research, allowing the entire community to identify the most clinically relevant and pressing questions; any idea can be translated into a study rather than limiting research to the ideas proposed by researchers in grant applications. Preliminary results from the CDCN and other organizations that have followed its Collaborative Network Approach suggest that this model is generalizable across rare diseases.

Design and Optimization of a Novel Strategy for the Local Treatment of Helicobacter pylori Infections

2020 ◽  
Author(s):  
Taddese Mekonnen Ambay ◽  
Philipp Schick ◽  
Michael Grimm ◽  
Maximilian Sager ◽  
Felix Schneider ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Local Treatment ◽  
Design And Optimization ◽  
Novel Strategy

L cell stimulation: a novel strategy for oral peptide delivery in incretin-based diabetes treatment

2020 ◽  
Author(s):  
Ana Beloqui ◽  
Francesco Suriano ◽  
Matthias Hul ◽  
Yining Xu ◽  
Véronique Préat ◽  
...  
Keyword(s):  
Peptide Delivery ◽  
Diabetes Treatment ◽  
Cell Stimulation ◽  
Oral Peptide Delivery ◽  
L Cell ◽  
Novel Strategy

Melatonin: a novel strategy for prevention of obesity and fat accumulation in peripheral organs through the improvements of circadian rhythms and antioxidative capacity

2020 ◽  
Vol 3 (1) ◽  
pp. 58-76 ◽  
Author(s):  
Bohan Rong ◽  
Qiong Wu ◽  
Chao Sun
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Regulatory Mechanisms ◽  
Antioxidative Capacity ◽  
Unicellular Alga ◽  
Peripheral Tissues ◽  
Peripheral Organs ◽  
Regulatory Effects ◽  
Novel Strategy

Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and its contribution to protection against oxidative stress in organisms including unicellular alga, animals and plants. Currently, the bio-regulatory effects of melatonin on the physiology of various peripheral tissues have drawn a great attention of scientists. Although melatonin was previously defined as a neurohormone secreted from pineal gland, recently it has been identified that virtually, every cell has the capacity to synthesize melatonin and the locally generated melatonin has multiple pathophysiological functions, including regulations of obesity and metabolic syndromes. Herein, we focus on the effects of melatonin on fat deposition in various peripheral organs/tissues. The two important regulatory mechanisms related to the topic, i.e., the improvements of circadian rhythms and antioxidative capacity will be thoroughly discussed since they are linked to several biomarkers involved in obesity and energy imbalance, including metabolism and immunity. Furthermore, several other functions of melatonin which may serve to prevent or promote obesity and energy dysmetabolism-induced pathological states are also addressed. The organs of special interest include liver, pancreas, skeletal muscle, adipose tissue and the gut microbiota.

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