scholarly journals Structural basis for the selective incorporation of an artificial nucleotide opposite a DNA adduct by a DNA polymerase

2017 ◽  
Vol 53 (94) ◽  
pp. 12704-12707 ◽  
Author(s):  
K. Betz ◽  
A. Nilforoushan ◽  
L. A. Wyss ◽  
K. Diederichs ◽  
S. J. Sturla ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Dna Adduct ◽  
Structural Basis ◽  
X Ray ◽  
X Ray Crystallography ◽  
Selective Incorporation

The structural basis for selective incorporation of BenziMP opposite O6-MeG by KlenTaq DNA polymerase is elucidated by X-ray crystallography.

scholarly journals Insights into the Structures of DNA Damaged by Hydroxyl Radical: Crystal Structures of DNA Duplexes Containing 5-Formyluracil

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Masaru Tsunoda ◽  
Takeshi Sakaue ◽  
Satoko Naito ◽  
Tomoko Sunami ◽  
Naoko Abe ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Dna Polymerase ◽  
Hydroxyl Radicals ◽  
Base Pair ◽  
Structural Basis ◽  
Dna Duplexes ◽  
X Ray ◽  
X Ray Crystallography ◽  
Guanine Base ◽  
New Type

Hydroxyl radicals are potent mutagens that attack DNA to form various base and ribose derivatives. One of the major damaged thymine derivatives is 5-formyluracil (fU), which induces pyrimidine transition during replication. In order to establish the structural basis for such mutagenesis, the crystal structures of two kinds of DNA d(CGCGRATfUCGCG) with R = A/G have been determined by X-ray crystallography. The fU residues form a Watson-Crick-type pair with A and two types of pairs (wobble and reversed wobble) with G, the latter being a new type of base pair between ionized thymine base and guanine base.In silicostructural modeling suggests that the DNA polymerase can accept the reversed wobble pair with G, as well as the Watson-Crick pair with A.

scholarly journals Structural basis for the binding of SNAREs to the multisubunit tethering complex Dsl1

2020 ◽  
Author(s):  
Sophie M. Travis ◽  
Kevin DAmico ◽  
I-Mei Yu ◽  
Safraz Hamid ◽  
Gabriel Ramirez-Arellano ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Relative Orientation ◽  
Snare Complex ◽  
Structural Basis ◽  
Binding Modes ◽  
Range Interaction ◽  
X Ray ◽  
X Ray Crystallography ◽  
Long Range Interaction ◽  
Target Membrane

AbstractMultisubunit tethering complexes (MTCs) are large (250 to >750 kDa), conserved macromolecular machines that are essential for SNARE-mediated membrane fusion in all eukaryotes. MTCs are thought to function as organizers of membrane trafficking, mediating the initial, long-range interaction between a vesicle and its target membrane and promoting the formation of membrane-bridging SNARE complexes. Previously, we reported the structure of the Dsl1 complex, the simplest known MTC, which is essential for COPI-mediated transport from the Golgi to the endoplasmic reticulum (ER). This structure suggested how the Dsl1 complex might function to tether a vesicle to its target membrane by binding at one end to the COPI coat and at the other end to ER SNAREs. Here, we use x-ray crystallography to investigate these Dsl1-SNARE interactions in greater detail. The Dsl1 complex comprises three subunits that together form a two-legged structure with a central hinge. Our results show that distal regions of each leg bind N-terminal Habc domains of the ER SNAREs Sec20 (a Qb-SNARE) and Use1 (a Qc-SNARE). The observed binding modes appear to anchor the Dsl1 complex to the ER target membrane while simultaneously ensuring that both SNAREs are in open conformations with their SNARE motifs available for assembly. The proximity of the two SNARE motifs, and therefore their ability to enter the same SNARE complex, depends on the relative orientation of the two Dsl1 legs.

scholarly journals Revealing an Internal Stabilization Deficiency in the DNA Polymerase β K289M Cancer Variant through the Combined Use of Chemical Biology and X-ray Crystallography

Biochemistry ◽  
2020 ◽  
Vol 59 (8) ◽  
pp. 955-963
Author(s):  
Vinod K. Batra ◽  
Khadijeh S. Alnajjar ◽  
Joann B. Sweasy ◽  
Charles E. McKenna ◽  
Myron F. Goodman ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Chemical Biology ◽  
Dna Polymerase Β ◽  
X Ray ◽  
X Ray Crystallography ◽  
Internal Stabilization ◽  
Combined Use

scholarly journals Crystal structure of glycosyltrehalose synthase fromSulfolobus shibataeDSM5389

2018 ◽  
Vol 74 (11) ◽  
pp. 741-746
Author(s):  
Nobuo Okazaki ◽  
Michael Blaber ◽  
Ryota Kuroki ◽  
Taro Tamada
Keyword(s):  
Crystal Structure ◽  
Amino Acids ◽  
Catalytic Mechanism ◽  
Catalytic Domain ◽  
Structural Basis ◽  
Hyperthermophilic Archaeon ◽  
X Ray ◽  
X Ray Crystallography ◽  
Sulfolobus Shibatae ◽  
Glucosidic Bond

Glycosyltrehalose synthase (GTSase) converts the glucosidic bond between the last two glucose residues of amylose from an α-1,4 bond to an α-1,1 bond, generating a nonreducing glycosyl trehaloside, in the first step of the biosynthesis of trehalose. To better understand the structural basis of the catalytic mechanism, the crystal structure of GTSase from the hyperthermophilic archaeonSulfolobus shibataeDSM5389 (5389-GTSase) has been determined to 2.4 Å resolution by X-ray crystallography. The structure of 5389-GTSase can be divided into five domains. The central domain contains the (β/α)8-barrel fold that is conserved as the catalytic domain in the α-amylase family. Three invariant catalytic carboxylic amino acids in the α-amylase family are also found in GTSase at positions Asp241, Glu269 and Asp460 in the catalytic domain. The shape of the catalytic cavity and the pocket size at the bottom of the cavity correspond to the intramolecular transglycosylation mechanism proposed from previous enzymatic studies.

scholarly journals Structural Basis for Norovirus Inhibition by Human Milk Oligosaccharides

2016 ◽  
Vol 90 (9) ◽  
pp. 4843-4848 ◽  
Author(s):  
Stefan Weichert ◽  
Anna Koromyslova ◽  
Bishal K. Singh ◽  
Satoko Hansman ◽  
Stefan Jennewein ◽  
...  
Keyword(s):  
Human Milk ◽  
Blood Group ◽  
Structural Basis ◽  
Blood Group Antigens ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
X Ray ◽  
X Ray Crystallography ◽  
Naturally Occurring

Histo-blood group antigens (HBGAs) are important binding factors for norovirus infections. We show that two human milk oligosaccharides, 2′-fucosyllactose (2′FL) and 3-fucosyllactose (3FL), could block norovirus from binding to surrogate HBGA samples. We found that 2′FL and 3FL bound at the equivalent HBGA pockets on the norovirus capsid using X-ray crystallography. Our data revealed that 2′FL and 3FL structurally mimic HBGAs. These results suggest that 2′FL and 3FL might act as naturally occurring decoys in humans.

scholarly journals The search for a structural basis for therapeutic intervention against the SARS coronavirus

2007 ◽  
Vol 64 (1) ◽  
pp. 204-213 ◽  
Author(s):  
Mark Bartlam ◽  
Xiaoyu Xue ◽  
Zihe Rao
Keyword(s):  
Infectious Disease ◽  
Severe Acute Respiratory Syndrome ◽  
Structural Biology ◽  
Therapeutic Intervention ◽  
Protein Structures ◽  
Structural Basis ◽  
X Ray ◽  
X Ray Crystallography ◽  
Main Protease ◽  
Underlying Mechanisms

The 2003 outbreak of severe acute respiratory syndrome (SARS), caused by a previously unknown coronavirus called SARS-CoV, had profound social and economic impacts worldwide. Since then, structure–function studies of SARS-CoV proteins have provided a wealth of information that increases our understanding of the underlying mechanisms of SARS. While no effective therapy is currently available, considerable efforts have been made to develop vaccines and drugs to prevent SARS-CoV infection. In this review, some of the notable achievements made by SARS structural biology projects worldwide are examined and strategies for therapeutic intervention are discussed based on available SARS-CoV protein structures. To date, 12 structures have been determined by X-ray crystallography or NMR from the 28 proteins encoded by SARS-CoV. One key protein, the SARS-CoV main protease (Mpro), has been the focus of considerable structure-based drug discovery efforts. This article highlights the importance of structural biology and shows that structures for drug design can be rapidly determined in the event of an emerging infectious disease.

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