Crystal structures of the chromosomal proteins Sso7d/Sac7d bound to DNA containing T-G mismatched base-pairs

AA·TT and GA·TC dinucleotide steps in B-DNA-type oligomeric crystal structures and in protein-bound DNA fragments (solved using data with resolution <2.6 Å) show very small variations in their local dinucleotide geometries. A detailed analysis of these crystal structures reveals that in AA·TT and GA·TC steps the electropositive C2—H2 group of adenine is in very close proximity to the keto O atoms of both the pyrimidine bases in the antiparallel strand of the duplex structure, suggesting the possibility of intra-base pair as well as cross-strand inter-base pair C—H...O hydrogen bonds in the DNA minor groove. The C2—H2...O2 hydrogen bonds in the A·T base pairs could be a natural consequence of Watson–Crick pairing. However, the cross-strand interactions between the bases at the 3′-end of the AA·TT and GA·TC steps obviously arise owing to specific local geometry of these steps, since a majority of the H2...O2 distances in both data sets are considerably shorter than their values in the uniform fibre model (3.3 Å) and many are even smaller than the sum of the van der Waals radii. The analysis suggests that in addition to already documented features such as the large propeller twist of A·T base pairs and the hydration of the minor groove, these C2—H2...O2 cross-strand interactions may also play a role in the narrowing of the minor groove in A-tract regions of DNA and help explain the high structural rigidity and stability observed for poly(dA)·poly(dT).

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Frequency and hydrogen bonding of nucleobase homopairs in small molecule crystals

Nucleic Acids Research ◽

10.1093/nar/gkaa629 ◽

2020 ◽

Vol 48 (15) ◽

pp. 8302-8319

Author(s):

Małgorzata Katarzyna Cabaj ◽

Paulina Maria Dominiak

Keyword(s):

Hydrogen Bonding ◽

Hydrogen Bonds ◽

Crystal Structures ◽

Small Molecule ◽

Base Pair ◽

Base Pairs ◽

Standard Pattern ◽

Planar Structures ◽

Structural Database ◽

Derivatives Of

Abstract We used the high resolution and accuracy of the Cambridge Structural Database (CSD) to provide detailed information regarding base pairing interactions of selected nucleobases. We searched for base pairs in which nucleobases interact with each other through two or more hydrogen bonds and form more or less planar structures. The investigated compounds were either free forms or derivatives of adenine, guanine, hypoxanthine, thymine, uracil and cytosine. We divided our findings into categories including types of pairs, protonation patterns and whether they are formed by free bases or substituted ones. We found base pair types that are exclusive to small molecule crystal structures, some that can be found only in RNA containing crystal structures and many that are native to both environments. With a few exceptions, nucleobase protonation generally followed a standard pattern governed by pKa values. The lengths of hydrogen bonds did not depend on whether the nucleobases forming a base pair were charged or not. The reasons why particular nucleobases formed base pairs in a certain way varied significantly.

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Intrastrand backbone-nucleobase interactions stabilize unwound right-handed helical structures of heteroduplexes of L-aTNA/RNA and SNA/RNA

Communications Chemistry ◽

10.1038/s42004-020-00400-2 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Yukiko Kamiya ◽

Tadashi Satoh ◽

Atsuji Kodama ◽

Tatsuya Suzuki ◽

Keiji Murayama ◽

...

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Crystal Structures ◽

Prebiotic Chemistry ◽

Basic Research ◽

Structural Features ◽

Helical Structures ◽

Base Pairs ◽

Triplex Structure ◽

Rna And Dna

Abstract Xeno nucleic acids, which are synthetic analogues of natural nucleic acids, have potential for use in nucleic acid drugs and as orthogonal genetic biopolymers and prebiotic precursors. Although few acyclic nucleic acids can stably bind to RNA and DNA, serinol nucleic acid (SNA) and L-threoninol nucleic acid (L-aTNA) stably bind to them. Here we disclose crystal structures of RNA hybridizing with SNA and with L-aTNA. The heteroduplexes show unwound right-handed helical structures. Unlike canonical A-type duplexes, the base pairs in the heteroduplexes align perpendicularly to the helical axes, and consequently helical pitches are large. The unwound helical structures originate from interactions between nucleobases and neighbouring backbones of L-aTNA and SNA through CH–O bonds. In addition, SNA and L-aTNA form a triplex structure via C:G*G parallel Hoogsteen interactions with RNA. The unique structural features of the RNA-recognizing mode of L-aTNA and SNA should prove useful in nanotechnology, biotechnology, and basic research into prebiotic chemistry.

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Supramolecular architectures in two 1:1 cocrystals of 5-fluorouracil with 5-bromothiophene-2-carboxylic acid and thiophene-2-carboxylic acid

Acta Crystallographica Section C Structural Chemistry ◽

10.1107/s2053229617007550 ◽

2017 ◽

Vol 73 (6) ◽

pp. 481-485 ◽

Cited By ~ 1

Author(s):

Marimuthu Mohana ◽

Packianathan Thomas Muthiah ◽

Colin D. McMillen

Keyword(s):

Solid State ◽

Carboxylic Acid ◽

Hydrogen Bonds ◽

Crystal Structures ◽

X Ray Diffraction ◽

Base Pairs ◽

X Ray ◽

Supramolecular Architectures ◽

Acid Acid ◽

Carboxylic Acid Dimer

In solid-state engineering, cocrystallization is a strategy actively pursued for pharmaceuticals. Two 1:1 cocrystals of 5-fluorouracil (5FU; systematic name: 5-fluoro-1,3-dihydropyrimidine-2,4-dione), namely 5-fluorouracil–5-bromothiophene-2-carboxylic acid (1/1), C5H3BrO2S·C4H3FN2O2, (I), and 5-fluorouracil–thiophene-2-carboxylic acid (1/1), C4H3FN2O2·C5H4O2S, (II), have been synthesized and characterized by single-crystal X-ray diffraction studies. In both cocrystals, carboxylic acid molecules are linked through an acid–acid R 2 2(8) homosynthon (O—H...O) to form a carboxylic acid dimer and 5FU molecules are connected through two types of base pairs [homosynthon, R 2 2(8) motif] via a pair of N—H...O hydrogen bonds. The crystal structures are further stabilized by C—H...O interactions in (II) and C—Br...O interactions in (I). In both crystal structures, π–π stacking and C—F...π interactions are also observed.

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Crystal structure of a DNA duplex containing four Ag(i) ions in consecutive dinuclear Ag(i)-mediated base pairs: 4-thiothymine–2Ag(i)–4-thiothymine

Chemical Communications ◽

10.1039/c7cc06153f ◽

2017 ◽

Vol 53 (86) ◽

pp. 11747-11750 ◽

Cited By ~ 16

Author(s):

Jiro Kondo ◽

Toru Sugawara ◽

Hisao Saneyoshi ◽

Akira Ono

Keyword(s):

Crystal Structure ◽

Crystal Structures ◽

Dna Duplexes ◽

Dna Duplex ◽

Base Pairs

The crystal structures of 4-thiothymine–2AgI–4-thiothymine base pairs in B-form DNA duplexes have been solved.

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Covalent Analogues of DNA Base-Pairs and Triplets V. Synthesis of Purine-Purine and Purine-Pyrimidine Conjugates Connected by Diverse Types of Acyclic Carbon Linkages

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20021560 ◽

2002 ◽

Vol 67 (10) ◽

pp. 1560-1578 ◽

Cited By ~ 18

Author(s):

Michal Hocek ◽

Hana Dvořáková ◽

Ivana Císařová

Keyword(s):

Single Crystal ◽

Crystal Structures ◽

Base Pair ◽

Cross Coupling ◽

X Ray Diffraction ◽

Base Pairs ◽

X Ray ◽

Dna Base ◽

Dna Base Pairs ◽

Purine Pyrimidine

The title 1,2-bis(purin-6-yl)acetylenes, -diacetylenes, -ethylenes and -ethanes were prepared as covalent base-pair analogues starting from 6-ethynylpurines and 6-iodopurines by the Sonogashira cross-coupling or oxidative alkyne-dimerization reactions followed by hydrogenations. 6-[(1,3-Dimethyluracil-5-yl)ethynyl]purine (11) was prepared analogously and hydrogenated to the corresponding purine-pyrimidine conjugates linked via vinylene and ethylene linkers. Unlike the cytostatic bis(purin-6-yl)acetylenes and -diacetylenes, the purine-pyrimidine conjugates were inactive. Crystal structures of bis(purin-6-yl)acetylene 6a, -diacetylene 8a and -ethane 5a were determined by single-crystal X-ray diffraction.

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Mismodeled purines: implicit alternates and hidden Hoogsteens

Acta Crystallographica Section D Structural Biology ◽

10.1107/s2059798317013729 ◽

2017 ◽

Vol 73 (10) ◽

pp. 852-859 ◽

Cited By ~ 5

Author(s):

Bradley J. Hintze ◽

Jane S. Richardson ◽

David C. Richardson

Keyword(s):

Crystal Structures ◽

Electron Density ◽

Opposite Direction ◽

Dna Sequences ◽

Occurrence Rate ◽

Difference Electron Density ◽

Base Pairs ◽

Manual Inspection ◽

Density Peaks

Hoogsteen base pairs are seen in DNA crystal structures, but only rarely. This study tests whether Hoogsteens or othersynpurines are either under-modeled or over-modeled, which are known problems for rare conformations. Candidate purines needing asyn/anti180° flip were identified by diagnostic patterns of difference electron-density peaks. Manual inspection narrowed 105 flip candidates to 20 convincing cases, all at ≤2.7 Å resolution. Rebuilding and refinement confirmed that 14 of these were authentic purine flips. Seven examples are modeled as Watson–Crick base pairs but should be Hoogsteens (commonest at duplex termini), and three had the opposite issue.Syn/antiflips were also needed for some single-stranded purines. Five of the 20 convincing cases arose from an unmodeled alternate duplex running in the opposite direction. These are in semi-palindromic DNA sequences bound by a homodimeric protein and show flipped-purine-like difference peaks at residues where the palindrome is imperfect. This study documents types of incorrect modeling which are worth avoiding. However, the primary conclusions are that such mistakes are infrequent, the bias towards fittingantipurines is very slight, and the occurrence rate of Hoogsteen base pairs in DNA crystal structures remains unchanged from earlier estimates at ∼0.3%.

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Structural variability of CG-rich DNA 18-mers accommodating double T–T mismatches

Acta Crystallographica Section D Structural Biology ◽

10.1107/s2059798320014151 ◽

2020 ◽

Vol 76 (12) ◽

pp. 1233-1243

Author(s):

Petr Kolenko ◽

Jakub Svoboda ◽

Jiří Černý ◽

Tatsiana Charnavets ◽

Bohdan Schneider

Keyword(s):

Crystal Structures ◽

Bacterial Species ◽

Crystal Data ◽

Temperature Dependent ◽

Base Pairs ◽

Biologically Relevant ◽

Dynamic Temperature ◽

Dna Crystals ◽

Helical Geometry ◽

Work Knowledge

Solution and crystal data are reported for DNA 18-mers with sequences related to those of bacterial noncoding single-stranded DNA segments called repetitive extragenic palindromes (REPs). Solution CD and melting data showed that the CG-rich, near-palindromic REPs from various bacterial species exhibit dynamic temperature-dependent and concentration-dependent equilibria, including architectures compatible with not only hairpins, which are expected to be biologically relevant, but also antiparallel duplexes and bimolecular tetraplexes. Three 18-mer oligonucleotides named Hpar-18 (PDB entry 6rou), Chom-18 (PDB entry 6ros) and its brominated variant Chom-18Br (PDB entry 6ror) crystallized as isomorphic right-handed A-like duplexes. The low-resolution crystal structures were solved with the help of experimental phases for Chom-18Br. The center of the duplexes is formed by two successive T–T noncanonical base pairs (mismatches). They do not deform the double-helical geometry. The presence of T–T mismatches prompted an analysis of the geometries of these and other noncanonical pairs in other DNA crystals in terms of their fit to the experimental electron densities (RSCC) and their geometric fit to the NtC (dinucleotide conformational) classes (https://dnatco.datmos.org/). Throughout this work, knowledge of the NtC classes was used to refine and validate the crystal structures, and to analyze the mismatches.

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Revealing A-T and G-C Hoogsteen base pairs in stressed protein-bound duplex DNA

10.1101/2021.06.05.447203 ◽

2021 ◽

Author(s):

Honglue Shi ◽

Issac Kimsey ◽

Hsuan-Fu Liu ◽

Uyen Pham ◽

Maria Schumacher ◽

...

Keyword(s):

Crystal Structures ◽

Genetic Information ◽

Double Helix ◽

Building Blocks ◽

Base Pairs ◽

Dna Complexes ◽

Damage Repair ◽

Functional Complexity ◽

Dna Double Helix ◽

Broad Role

Watson-Crick base pairs (bps) are the fundamental unit of genetic information and the building blocks of the DNA double helix. However, A-T and G-C can also form alternative 'Hoogsteen' bps, expanding the functional complexity of DNA. We developed 'Hoog-finder', which uses structural fingerprints to rapidly screen Hoogsteen bps, which may have been mismodeled as Watson-Crick in crystal structures of protein-DNA complexes. We uncovered seventeen Hoogsteen bps, seven of which were in complex with six proteins never before shown to bind Hoogsteen bps. The Hoogsteen bps occur near mismatches, nicks, and lesions and some appear to participate in recognition and damage repair. Our results suggest a potentially broad role for Hoogsteen bps in stressed regions of the genome and call for a community-wide effort to identify these bps in current and future crystal structures of DNA and its complexes.

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How does Mg2+ modulate the RNA folding mechanism — a case study of G:C W:W Trans base pair

10.1101/098079 ◽

2017 ◽

Author(s):

Antarip Halder ◽

Rohit Roy ◽

Dhananjay Bhattacharyya ◽

Abhijit Mitra

Keyword(s):

Crystal Structures ◽

Base Pair ◽

Rna Structure ◽

Binding Modes ◽

Base Pairs ◽

Bonding Interaction ◽

Direct Binding ◽

And Function ◽

Experimental Geometry

AbstractReverse Watson-Crick G:C base pairs (G:C W:W Trans) occur frequently in different functional RNAs. It is one of the few base pairs whose gas phase optimized isolated geometry is inconsistent with the corresponding experimental geometry. Several earlier studies indicate that accumulation of positive charge near N7 of guanine, through posttranscriptional modification, direct protonation or coordination with Mg2+, can stabilize the experimental geometry. Interestingly, recent studies reveal significant variation in the position of putatively bound Mg2+. This, in conjunction with recently raised doubts regarding some of the Mg2+ assignments near the imino nitrogen of guanine, is suggestive of the existence of multiple Mg2+ binding modes for this base pair. Our detailed investigation of Mg2+ bound G:C W:W Trans pairs, occurring in high resolution RNA crystal structures, show that they occur in 14 different contexts, 8 out of which display Mg2+ binding at the Hoogsteen edge of guanine. Further examination of occurrences in these 8 contexts led to the characterization of three different Mg2+ binding modes, (i) direct binding via N7 coordination, (ii) direct binding via O6 coordination and (iii) binding via hydrogen bonding interaction with the first shell water molecules. In the crystal structures, the latter two modes are associated with a buckled and propeller twisted geometry of the base pair. Interestingly, respective optimized geometries of these different Mg2+ binding modes (optimized at B3LYP) are consistent with their corresponding experimental geometries. Subsequent interaction energy calculations at MP2 level, and decomposition of its components, suggest that for G:C W:W Trans, Mg2+ binding can fine tune the base pair geometries without compromising with their stability. Our results, therefore, underline the importance of the mode of binding of Mg2+ ions in shaping RNA structure, folding and function.

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