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Musashi-2 (MSI2) belongs to Musashi family of RNA binding proteins. Like Musashi-1 (MSI1), it is overexpressed in a variety of cancers and is a promising therapeutic target. Both MSI proteins contain two N-terminal RNA recognition motifs and play roles in post-transcriptional regulation of target mRNAs. Previously, we have identified several inhibitors of MSI1, all of which bind to MSI2 as well. In order to design MSI2 specific inhibitors and compare the differences of binding mode of the inhibitors, we set out to solve the structure of MSI2-RRM1, the key motif that is responsible for the binding. Here we report the crystal structure and the first NMR solution structure of MSI2-RRM1, and compare these to the structures of MSI1-RBD1 and other RNA binding proteins. A high degree of structural similarity was observed between the crystal and solution NMR structures. MSI2-RRM1 shows a highly similar overall folding topology to MSI1-RBD1 and other RNA binding proteins. The structural information of MSI2-RRM1 will be helpful for understanding MSI2-RNA interaction and for guiding rational drug design of MSI2 specific inhibitors. This article is protected by copyright. All rights reserved.
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G-quadruplexes (G4) are secondary structures of nucleic acids that can form in cells and have diverse biological functions. Several biologically important proteins interact with G-quadruplexes, of whi...
Hygromycin B (HygB) is one of the aminoglycoside antibiotics, and it is widely used as a reagent in molecular-biology experiments. Two kinases are known to inactivate HygB through phosphorylation: ami...
Lon protease is evolutionarily conserved in prokaryotes and eukaryotic organelles. The primary function of Lon is to selectively degrade abnormal and certain regulatory proteins to maintain the homeos...
The DcCoV UAE-HKU23 coronavirus is a newly-found betacoronavirus (betaCoV) that can infect human cells. The viral spike protein plays pivotal roles in mediating receptor-recognition and membrane-fusio...
Analogous to the B- and Z-DNA structures in double-helix DNA, there exist both right- and left-handed quadruple-helix (G-quadruplex) DNA. Numerous conformations of right-handed and a few left-handed G...
This is a Phase 3, randomized, double-blind, controlled, parallel-group, multicenter clinical trial with co-crystal E-58425 compared to tramadol, to celecoxib, and to placebo. The primary ...
Cystadrops® is currently indicated in adults and children from 2 years of age diagnosed with cystinosis with corneal crystal accumulation observed. However administration of Cystadrops®...
The primary objective of this study is to compare the concentration in human tears of levofloxacin and the active comparators at 15 minutes, 2,6, 12, and 24 hours after instillation of a s...
It is suggested that P-wave terminal force (Ptf), a product of the amplitude (PAM) and the duration (PT) of the terminal phase of P-wave in lead V1, shows early delay in left atrial conduc...
The purpose of this study is to develop and validate a deep learning algorithm to realize automatic recognition of colonic segments under conventional colonoscopy. Then, evaluate the accur...
Hypertonic sodium chloride solution. A solution having an osmotic pressure greater than that of physiologic salt solution (0.9 g NaCl in 100 ml purified water).
A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.
A family of RRM proteins which contain two N-terminal RNA RECOGNITION MOTIF (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 amino acids between the second and third RRM domains. They regulate pre-mRNA ALTERNATIVE SPLICING and also function in RNA EDITING and PROTEIN BIOSYNTHESIS.
Organs and other anatomical structures of non-human vertebrate and invertebrate animals.
An N-terminal acetyltransferase subtype that consists of the Naa20p catalytic subunit and the Naa25p auxiliary subunit. The structure of this enzyme is conserved between YEASTS and HUMAN. It has specificity for the N-terminal METHIONINE of peptides where the next amino acid in the chain is either ASPARTATE; GLUTAMATE; ASPARAGINE; OR GLUTAMINE.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...