Abstract:
:RNA repeat expansions cause a host of incurable, genetically defined diseases. The most common class of RNA repeats consists of trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics. The 1 × 1 internal loops of r(3×CAG) are stabilized by one-hydrogen bond (cis Watson-Crick/Watson-Crick) AA pairs, while those of r(3×CUG) prefer one- or two-hydrogen bond (cis Watson-Crick/Watson-Crick) UU pairs. Assigned chemical shifts for the residues depended on the identity of neighbors or next nearest neighbors. Additional insights into the dynamics of these RNA constructs were gained by molecular dynamics simulations and a discrete path sampling method. Results indicate that the global structures of the RNA are A-form and that the loop regions are dynamic. The results will be useful for understanding the dynamic trajectory of these RNA repeats but also may aid in the development of therapeutics.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Chen JL,VanEtten DM,Fountain MA,Yildirim I,Disney MDdoi
10.1021/acs.biochem.7b00252subject
Has Abstractpub_date
2017-07-11 00:00:00pages
3463-3474issue
27eissn
0006-2960issn
1520-4995journal_volume
56pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::To probe attitudinal features of the Ca(2+)-deficient site (site I) in the Ca2+ switch of cardiac troponin C (cTnC), we have examined steady-state fluorescence emission and polarization of a Trp26 inserted in a recombinant cardiac TnC (cTnC3.W) and compared these with the properties of the Ca(2+)-competent site I in s...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00002a022
更新日期:1995-01-17 00:00:00
abstract::PEP mutase catalyzes the conversion of phosphoenolpyruvate (PEP) to phosphonopyruvate in biosynthetic pathways leading to phosphonate secondary metabolites. A recent X-ray structure [Huang, K., Li, Z., Jia, Y., Dunaway-Mariano, D., and Herzberg, O. (1999) Structure (in press)] of the Mytilus edulis enzyme complexed wi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi990771j
更新日期:1999-10-26 00:00:00
abstract::G protein alpha subunits mediate activation of signaling pathways through G protein-coupled receptors (GPCR) by virtue of GTP-dependent conformational rearrangements. It is known that regions of disorder in crystal structures can be indicative of conformational flexibility within a molecule, and there are several such...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0255726
更新日期:2002-08-06 00:00:00
abstract::Miniproteins reduce the complexity of the protein-folding problem allowing systematic studies of contributions to protein folding and stabilization. Here, we describe the rational redesign of a miniprotein, PPα, comprising a polyproline II helix, a loop, and an α helix. The redesign provides a de novo framework for in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.9b00067
更新日期:2019-07-16 00:00:00
abstract::Steady-state kinetic parameters were determined for the human leukocyte elastase catalyzed hydrolysis of a series of peptide-based thiobenzyl esters and p-nitroanilides. The peptide units are MeOSuc-Val, MeOSuc-Alan-Pro-Val (n = 0-2), and MeOSuc-Alan-Pro-Ala (n = 1 or 2). The results of this study suggest five importa...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00379a015
更新日期:1987-03-10 00:00:00
abstract::Transported proteins often contain an extension sequence called the signal peptide. The alkaline phosphatase (PhoA) signal sequence represents a typical signal peptide for comparison to idealized sequences both in vivo and in vitro. We have designed a series of idealized signal sequences which vary in amino terminal c...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00031a012
更新日期:1995-08-08 00:00:00
abstract::We have used flash-detection optical and electron paramagnetic resonance spectroscopy to measure the kinetics and yield per flash of the photooxidation of cytochrome b559 and the yield per flash of the photooxidation of the tyrosine residue YD in Mn-depleted photosystem II (PSII) membranes at room temperature. The ini...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00490a014
更新日期:1990-09-25 00:00:00
abstract::A procedure for universal 13C and/or 15N labeling of microbial peptides which are produced by fermentation in complex media and its application to two food-preserving bacteriocins from lactic acid bacteria are described. Isotopic enrichment of nisin A (from Lactococcus lactis) and of leucocin A (from Leuconostoc gelid...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00052a039
更新日期:1993-01-12 00:00:00
abstract::The reactions of Rhodopseudomonas viridis cytochrome c2 and horse cytochrome c with Rps. viridis photosynthetic reaction centers were studied by using both single- and double-flash excitation. Single-flash excitation of the reaction centers resulted in rapid photooxidation of cytochrome c-556 in the cytochrome subunit...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00219a021
更新日期:1991-02-05 00:00:00
abstract::Bacterial L-asparaginases, enzymes that catalyze the hydrolysis of L-asparagine to aspartic acid, have been used for over 30 years as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia. Other substrates of asparaginases include L-glutamine, D-asparagine, and succinic acid monoamide. In this ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0029595
更新日期:2001-05-15 00:00:00
abstract::DNA gyrase and topoisomerase IV (Topo IV) are cellular targets of quinolone antibacterial drugs. The Ser-80 and the Glu-84 of the ParC subunit have been identified as mutational hotspots for quinolone resistance. Mutant Topo IV proteins containing a quinolone resistance-conferring mutation have been constructed, and t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026352v
更新日期:2002-10-01 00:00:00
abstract::The enzyme RhlI catalyzes the formation of N-butyrylhomoserine lactone from S-adenosylmethionine and N-butyrylacyl carrier protein. N-Butyrylhomoserine lactone serves as a quorum-sensing signal molecule in Pseudomonas aeruginosa, and is implicated in the regulation of many processes involved in bacterial virulence and...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048005m
更新日期:2005-03-01 00:00:00
abstract::Brd4 belongs to the BET family. It is a multifunctional protein involved in transcription, replication, the signal transduction pathway, and cell cycle progression. All of these functions are linked to its association with acetylated chromatin. With its tandem bromodomains, Brd4 avidly binds to diacetylated H4-AcK5/K1...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi8001659
更新日期:2008-06-17 00:00:00
abstract::In order to understand translocation in transcription, it is important to develop a continuous functional assay for RNA polymerase (RNAP) activity in vitro. Fluorescent derivatives of ATP, UTP, UpA, and CpA with aminonaphthalene-5-sulfonic acid (AmNS) attached to the nucleotide triphosphates via a gamma-phosphoramidat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00143a013
更新日期:1992-07-21 00:00:00
abstract::Thyroxine and analogues inhibit rat liver aminoacyl-tRNA synthetase activity for phenylalanine and tyrosine. A high yield purification of the major cytoplasmic form of phenylalanyl-tRNA synthetase (C1) and its characterization is reported. Polyribosome-bound and other sedimentable forms are found to be indistinguishab...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00647a017
更新日期:1976-01-27 00:00:00
abstract::Engineering proteins to withstand a broad range of conditions continues to be a coveted objective, holding the potential to advance biomedicine, industry, and our understanding of disease. One way of achieving this goal lies in elucidating the underlying interactions that define protein stability. It has been shown th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0600143
更新日期:2006-03-07 00:00:00
abstract::Endogenous DNA damage occurs at a rate of at least 20,000 lesions per cell per day. Base excision repair (BER) is a key pathway for maintaining genome stability. Several pol beta variants were identified as conferring resistance to 3'-azido-3'-deoxythymidine (AZT) in Escherichia coli (Kosa et al. (1999) J. Biol. Chem....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi702104y
更新日期:2008-08-05 00:00:00
abstract::Eukaryotic translation initiation factor 2B (eIF2B) is the guanine nucleotide exchange factor of the GTPase eIF2, which brings the initiator Met-tRNAi to the ribosome in the form of the eIF2-GTP·Met-tRNAi ternary complex (TC). The activity of eIF2B is inhibited by phosphorylation of its substrate eIF2 by several stres...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.7b00957
更新日期:2018-03-06 00:00:00
abstract::The three-dimensional solution structure of toxin FS2, a 60-residue polypeptide isolated from the venom of black mamba snake (Dendroaspis polylepis polylepis), has been determined by nuclear magnetic resonance spectroscopy. Using 600 NOE constraints and 55 dihedral angle constraints, a set of 20 structures obtained fr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00017a022
更新日期:1995-05-02 00:00:00
abstract::Factor V and factor Va binding to single bilayer phospholipid vesicles was investigated by light-scattering intensity measurements. This technique allows the measurement of free and phospholipid-bound protein concentrations from which equilibrium constants can be obtained. As controls, the Ca2+-dependent phospholipid ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00587a023
更新日期:1979-10-02 00:00:00
abstract::The structures of four isomorphous crystals of ternary complexes of chicken heart citrate synthase with D- or L-malate and acetyl coenzyme A or carboxymethyl coenzyme A have been determined by X-ray crystallography and fully refined at 1.9-A resolution. The structures show that both L-malate and D-malate bind in a ver...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00238a028
更新日期:1991-06-18 00:00:00
abstract::Sphingosine, sphinganine, and other long-chain (sphingoid) bases inhibit protein kinase C in vitro and block cellular responses to agonists that are thought to act via this enzyme. To gain further insight into the mechanism of this inhibition, a series of long-chain analogues differing in alkyl chain length (11-20 car...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00434a004
更新日期:1989-04-18 00:00:00
abstract::Isothiouronium compounds [Hoving, S., Bar-Shimon, M., Tijmes, J. J., Goldshleger, R., Tal, D. M., and Karlish, S. J. (1995) J. Biol. Chem. 270, 29788-29793] act as high-affinity competitive antagonists for Na(+) and K(+) (Rb(+)) on the renal Na(+)/K(+)-ATPase where they favor the E1 conformation. We have now character...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026071n
更新日期:2003-04-01 00:00:00
abstract::Sedimentation equilibrium and sedimentation velocity measurements demonstrate that turkey gizzard caldesmon is an elongated molecule of molecular mass 75 +/- 2 kDa. The frictional ratio (2.14) is consistent with a prolate ellipsoid of axial ratio 24, corresponding to an apparent length and width of 516 and 21.5 A, res...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00446a039
更新日期:1989-10-03 00:00:00
abstract::Surface plasmon resonance (SPR) detection technology was employed to investigate the kinetic mechanism of deoxyadenosine kinase from Mycoplasma mycoides ssp. mycoides SC. In our experimental approach, the enzyme was attached to the sensor surface, the reactants were injected in the mobile phase, and the product-enzyme...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0515523
更新日期:2006-01-17 00:00:00
abstract::Escherichia coli non-heme-binding ferritin A (EcFtnA) is a spherical cagelike protein that is composed of 24 identical subunits. EcFtnA dissociates into 2-mers under acidic conditions and can reassemble into the native structure when the pH is increased. To understand how electrostatic interactions influence the assem...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b01197
更新日期:2016-01-26 00:00:00
abstract::The use of cefoxitin, a poor substrate of the RTEM beta-lactamase, has allowed the kinetic and spectroscopic characterization of a covalent acyl-enzyme intermediate in the enzyme-catalyzed reaction. The rate of reappearance of catalytic activity in an enzyme sample diluted from an incubation with cefoxitin is nearly i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00554a012
更新日期:1980-06-24 00:00:00
abstract::The presence of a N-(2-deoxy-D-erythro pentofuranosyl)urea (henceforth referred to as deoxyribosylurea) residue, ring fragmentation product of a thymine, in a frameshift situation in the sequence 5'd(AGGACCACG).d(CGTGGurTCCT) has been studied by 1H and 31P nuclear magnetic resonance and molecular dynamics. At equilibr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi971202j
更新日期:1998-01-27 00:00:00
abstract::The conformation of the glycerol group of a number of diacyl and monoacyl (lyso) phospholipids differing in the chemical nature of the head group was studied by 1H high-resolution NMR and X-ray crystallography. The NMR measurements were carried out with solutions or micellar dispersions of the lipids in deuteriated or...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00426a014
更新日期:1988-12-27 00:00:00
abstract::The group-specific antigen was isolated from a type Ia group B streptococcal strain and is a complex polysaccharide composed of alpha-L-rhamnopyranosyl, alpha-D-galactopyranosyl, 2-acetamido-2-deoxy-beta-D-glucopyranosyl, D-glucitol, and phosphate residues. The complexity of the group B polysaccharide antigen is evide...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00376a020
更新日期:1987-01-27 00:00:00