Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D02209 (RSM)
 349 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Under physiological conditions, guanine-rich sequences of DNA and RNA can adopt stable and atypical four-stranded helical structures called G-quadruplexes (G4). Such G4 structures have been shown to occur in vivo and to play a role in various processes such as transcription, translation and telomere maintenance. Owing to their high-thermodynamic stability, resolution of G4 structures in vivo requires specialized enzymes. RHAU is a human RNA helicase of the DEAH-box family that exhibits a unique ATP-dependent G4-resolvase activity with a high affinity and specificity for its substrate in vitro. How RHAU recognizes G4-RNAs has not yet been established. Here, we show that the amino-terminal region of RHAU is essential for RHAU to bind G4 structures and further identify within this region the evolutionary conserved RSM (RHAU-specific motif) domain as a major affinity and specificity determinant. G4-resolvase activity and strict RSM dependency are also observed with CG9323, the Drosophila orthologue of RHAU, in the amino terminal region of which the RSM is the only conserved motif. Thus, these results reveal a novel motif in RHAU protein that plays an important role in recognizing and resolving G4-RNA structures, properties unique to RHAU among many known RNA helicases.
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PMID:Role of the amino terminal RHAU-specific motif in the recognition and resolution of guanine quadruplex-RNA by the DEAH-box RNA helicase RHAU. 2047 41

Chikungunya virus (CHIKV) infection is one of the major public health concerns, leading thousands of cases every year in rural as well as urban regions of several countries worldwide, few to mention are India, Philippines, Indonesia, and also in American countries. The structural and non-structural proteins of CHIKV are structurally and functionally similar to other alphaviruses such as Sindbis virus, Venezuelan Equine Encephalitis virus. The precursor protein of non-structural proteins is cleaved by proteolytic activity of non-structural protein (nsp2). This multifunctional nsp2 carry out nucleoside-triphosphatase (NTPase) and RNA helicase activity at its N-terminal and protease activity at C-terminal that makes it primarily a drug target to inhibit CHIKV replication. Until the current date, no suitable treatment for chikungunya infection is available. The introduction of a new drug into the market is a lengthy process, therefore, drug repurposing is now familiar approach that cut off the time and cost of drug discovery. In this study, we have implemented this approach with Food and Drug Administration (FDA) approved drugs and known cysteine protease inhibitors against CHIKV nsp2 protease using structure-based drug discovery. Our extensive docking and molecular dynamics simulations studies leads to two best interacting compounds, Ribostamycin sulfate and E-64, with utmost stable complexes at active site of nsp2 protease. Therefore, these compounds could be suitable for inhibiting CHIKV protease activity, and ultimately the viral replication.
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PMID:Targeting the nsp2 Cysteine Protease of Chikungunya Virus Using FDA Approved Library and Selected Cysteine Protease Inhibitors. 3144 66