Results 111 to 120 of about 2,237,466 (287)

Probing the activity modification space of the cysteine peptidase cathepsin K with novel allosteric modifiers.

PLoS ONE, 2014
Targeting allosteric sites is gaining increasing recognition as a strategy for modulating the activity of enzymes, especially in drug design. Here we investigate the mechanisms of allosteric regulation of cathepsin K as a representative of cysteine ...
Marko Novinec, Brigita Lenarčič, Antonio Baici   +2 more
doaj   +1 more source

Computation and Structure‐Guided Arginine Scanning Engineers a Hyperactive AP Endonuclease for Multiplex Viral RNA Sensing

Advanced Science, EarlyView.
Computational and structure‐guided arginine scanning rewires the DNA‐binding interface of APE1 to create APE1‐Evo, a hyperactive yet specific AP endonuclease. Integrated into the NAPTUNE‐V2.0 cascade, APE1‐Evo enables amplification‐free, multiplex viral RNA sensing for dengue virus and influenza A/B, highlighting a general strategy for engineering ...
Junlan Wang, Ting Wu, Feizuo Wang, Boyang Wang, Xin Yu Wong, Senfeng Zhang, Shengsheng Ma, Yao Liu, Fangyao Yao, Zhifeng Zeng, Siyuan Yang, Kunming Liu, Qi Wang, Yilong Wang, Yunxiang Zang, Xiaolong Wang, Xingxu Huang, Shao Li, Quanquan Ji, Tao Hu, Chunyi Hu   +20 more
wiley   +1 more source

Scheme of allosteric regulation of YfiN.

, 2013
Schematic representation of the putative allosteric regulation of YfiN based on homology modeling pointing to a LapD-like allosteric communication between the periplasmic and the cytosolic portions of the enzyme that is mediated by a conformational ...
Stefano Franceschini (488912), Alessandro Paiardini (59368), Silvia Fernicola (488911), Serena Rinaldo (459402), Valentina Stelitano (459399), Francesca Cutruzzolà (459401), Giorgio Giardina (182340)   +6 more
core   +1 more source

The Natural Product Corramycin Acts as a DNA Gyrase Poison and Overcomes Fluoroquinolone Resistance in Mycobacterium tuberculosis

Advanced Science, EarlyView.
Corramycin, a myxobacterial natural product antibiotic, exhibits potent bactericidal activity against multidrug‐resistant Mycobacterium tuberculosis. The compound hijacks bacterial transporters such as BacA and OppABCD to enter the cell and inhibits DNA synthesis through a previously unrecognized mode of DNA gyrase poisoning, locking the enzyme in an ...
Franziska Fries, Jennifer Herrmann, Michael Dal Molin, Yaëlle Wormser, Timo Risch, Yunsheng Gao, Gareth Prosser, Francesca Gubellini, Ariel Mechaly, Joshua B. Wallach, Anthony Castro, Arka Banerjee, Sari Rasheed, Alexander Horn, Mathias Müsken, Michael Kurz, Lindsay Sonnenkalb, Viola Dreyer, Stefan Niemann, Sönke Andres, Dirk Schnappinger, Uli Kazmaier, Norbert Reiling, Rolf Müller, Jan Rybniker, Stéphanie Petrella   +25 more
wiley   +1 more source

Targeting Tex10 Overcomes Oxaliplatin Resistance by Competitively Disrupting the Non‐Canonical BAF Complex in Colorectal Cancer

Advanced Science, EarlyView.
This study reveals that Tex10 drives oxaliplatin resistance in colorectal cancer by competitively binding BRD9 to disrupt the ncBAF complex, thereby suppressing AMBRA1 transcription and ULK1‐mediated autophagy. Gemcitabine is identified as a direct Tex10 inhibitor that restores autophagy and overcomes resistance.
Ping Xu, Jie Huang, Xiaojin Gao, Lin Deng, Yanheng Deng, Denglu Wang, Chunlei Yu, Yunxiang Zhang, Jingdong Li, Xiaocong Xiang   +9 more
wiley   +1 more source

Continuous Evolution System Based on Toxin–Antitoxin System Combined with Base Deaminase Accelerates the In Vivo Modification of Target Proteins

Advanced Science, EarlyView.
The promoted Escherichia coli‐assisted continuous evolution (PEACE) system operates through a stringent three step genetic circuit: target gene mutation via a deaminase–T7 RNA polymerase (T7 RNAP) fusion, coupling variant function to antitoxin expression, and growth based selection of surviving cells.
Xinyu Zhang, Zhanzhi Liu, Ying Xu, Mingjing Sun, Guangzhen Zhou, Deming Rao, Xiaoqian Chen, Sheng Wang, Zhigang Li, Yan Huang, Jing Wu   +10 more
wiley   +1 more source

A Novel Pak1 Activator Ameliorates ER Stress for HFpEF Therapy

Advanced Science, EarlyView.
Chronic metabolic stress is a major contributor to HFpEF progression. Under prolonged metabolic stress, Pak1 activity becomes impaired, contributing to disrupted ER proteostasis, cardiomyocyte apoptosis, fibrosis, and diastolic dysfunction. Mechanistically, Pak1 overexpression activates the ERK1/2–MNK1–eIF4E signaling axis, promotes translational ...
Honglin Xu, Hongyuan Zhang, Tayyiba Azam, Susanne S. Hille, Yingjuan Liu, Min Zi, Jiaqing Lang, He Yu, Yujia Cao, Bernard D. Keavney, Tamer M. A. Mohamed, Jessica M. Miller, Riham R. E. Abouleisa, Ming Xu, Elizabeth J. Cartwright, Oliver J. Müller, Ming Lei, Xin Wang   +17 more
wiley   +1 more source

DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated‐Acute Kidney Injury

Advanced Science, EarlyView.
This study identifies a potential therapeutic approach for sepsis‐associated acute kidney injury (SA‐AKI). We found that during SA‐AKI, reduced expression of DDX3x in renal tubular epithelial cells mediates histone delactylation, which in turn upregulates NINJ1 transcription and triggers tubular cell death. Conversely, Odetiglucan confers protection by
Hongyu Liang, Jihong Jiang, Huanxin Yin, Chunyan Liu, Hongjun Huang, Yan Luo, Minmin Zhu, Qiuyun Wang   +7 more
wiley   +1 more source

The multifaceted allosteric regulation of Aurora kinase A [PDF]

Biochemical Journal, 2018
The protein kinase Aurora A (AurA) is essential for the formation of bipolar mitotic spindles in all eukaryotic organisms. During spindle assembly, AurA is activated through two different pathways operating at centrosomes and on spindle microtubules.
openaire   +2 more sources

Transcription Factor HOXC11 Drives Colorectal Cancer Progression and Metastasis via CAMK2A‐Dependent CXCL5 Upregulation

Advanced Science, EarlyView.
HOXC11 drives colorectal cancer progression by transcriptionally activating CAMK2A, which triggers NF‐κB–dependent CXCL5 upregulation. CXCL5–CXCR2 signaling further reinforces HOXC11 expression through the ERK1/2–SP1 axis, forming a prometastatic positive feedback loop that is effectively disrupted by combined CAMK2A and CXCR2 inhibition.
Qingyang Sun, Hengjie Xu, Sheng Yang, Jiahui Zhou, Chuanxin Tian, Hongxu Nie, Chi Jin, Tuo Wang, Zhihao Chen, Junwei Tang, Yifei Feng, Xiaowei Wang, Yueming Sun   +12 more
wiley   +1 more source