Insights into RNA binding by the anticancer drug cisplatin from the crystal structure of cisplatin-modified ribosome

The structure of the anticancer drug carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, C5H9Cl2N3O2) was successfully determined from laboratory X-ray powder diffraction data recorded at 278 K and at 153 K. Carmustine crystallizes in the orthorhombic space group P212121 with Z = 4. The lattice parameters are a = 19.6935(2) Å, b = 9.8338(14) Å, c = 4.63542(6) Å, V = 897.71(2) Å³ at 153 K, and a = 19.8522(2) Å, b = 9.8843(15) Å, c = 4.69793(6) Å, V = 921.85(2) Å³ at 278 K. The Rietveld fits are very good, with low R-values and smooth difference curves of calculated and experimental powder data. The molecules form a one-dimensional hydrogen bond pattern. At room temperature, the investigated commercial sample of carmustine was amorphous.

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Crystal Structure of Ribosomal Protein L30e from the Extreme ThermophileThermococcus celer: Thermal Stability and RNA Binding†,‡

Biochemistry ◽

10.1021/bi027131s ◽

2003 ◽

Vol 42 (10) ◽

pp. 2857-2865 ◽

Cited By ~ 9

Author(s):

Yu Wai Chen ◽

Mark Bycroft ◽

Kam-Bo Wong

Keyword(s):

Crystal Structure ◽

Thermal Stability ◽

Ribosomal Protein ◽

Rna Binding

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Crystal structure of prokaryotic ribosomal protein L9: a bi-lobed RNA-binding protein.

The EMBO Journal ◽

10.1002/j.1460-2075.1994.tb06250.x ◽

1994 ◽

Vol 13 (1) ◽

pp. 205-212 ◽

Cited By ~ 72

Author(s):

D.W. Hoffman ◽

C. Davies ◽

S.E. Gerchman ◽

J.H. Kycia ◽

S.J. Porter ◽

...

Keyword(s):

Crystal Structure ◽

Ribosomal Protein ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Ribosomal Protein L9

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Crystal structure of Hfq from Bacillus subtilis in complex with SELEX-derived RNA aptamer: insight into RNA-binding properties of bacterial Hfq

Nucleic Acids Research ◽

10.1093/nar/gkr892 ◽

2011 ◽

Vol 40 (4) ◽

pp. 1856-1867 ◽

Cited By ~ 59

Author(s):

Tatsuhiko Someya ◽

Seiki Baba ◽

Mai Fujimoto ◽

Gota Kawai ◽

Takashi Kumasaka ◽

...

Keyword(s):

Crystal Structure ◽

Bacillus Subtilis ◽

Rna Binding ◽

Rna Aptamer ◽

Binding Properties ◽

Insight Into

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Crystal Structure of Human Rpp20/Rpp25 Reveals Quaternary Level Adaptation of the Alba Scaffold as Structural Basis for Single-stranded RNA Binding

Journal of Molecular Biology ◽

10.1016/j.jmb.2018.03.029 ◽

2018 ◽

Vol 430 (10) ◽

pp. 1403-1416 ◽

Cited By ~ 3

Author(s):

Clarence W. Chan ◽

Benjamin R. Kiesel ◽

Alfonso Mondragón

Keyword(s):

Crystal Structure ◽

Rna Binding ◽

Structural Basis

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Structural basis of the zinc-induced cytoplasmic aggregation of the RNA-binding protein SFPQ

Nucleic Acids Research ◽

10.1093/nar/gkaa076 ◽

2020 ◽

Vol 48 (6) ◽

pp. 3356-3365 ◽

Cited By ~ 4

Author(s):

Jie Huang ◽

Mitchell Ringuet ◽

Andrew E Whitten ◽

Sofia Caria ◽

Yee Wa Lim ◽

...

Keyword(s):

Crystal Structure ◽

Cortical Neurons ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Zinc Binding ◽

Structural Basis ◽

Rna Biogenesis ◽

Cytoplasmic Accumulation ◽

Nucleocytoplasmic Distribution

Abstract SFPQ is a ubiquitous nuclear RNA-binding protein implicated in many aspects of RNA biogenesis. Importantly, nuclear depletion and cytoplasmic accumulation of SFPQ has been linked to neuropathological conditions such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Here, we describe a molecular mechanism by which SFPQ is mislocalized to the cytoplasm. We report an unexpected discovery of the infinite polymerization of SFPQ that is induced by zinc binding to the protein. The crystal structure of human SFPQ in complex with zinc at 1.94 Å resolution reveals intermolecular interactions between SFPQ molecules that are mediated by zinc. As anticipated from the crystal structure, the application of zinc to primary cortical neurons induced the cytoplasmic accumulation and aggregation of SFPQ. Mutagenesis of the three zinc-coordinating histidine residues resulted in a significant reduction in the zinc-binding affinity of SFPQ in solution and the zinc-induced cytoplasmic aggregation of SFPQ in cultured neurons. Taken together, we propose that dysregulation of zinc availability and/or localization in neuronal cells may represent a mechanism for the imbalance in the nucleocytoplasmic distribution of SFPQ, which is an emerging hallmark of neurodegenerative diseases including AD and ALS.

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