Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Crystal structure of Z-DNA in complex with the polyamine putrescine and potassium cations at ultra-high resolution.

ABSTRACT: The X-ray crystal structure of the d(CGCGCG)₂/putrescine(2+)/K⁺ complex has been determined at 0.60 Å resolution. Stereochemical restraints were used only for the putrescinium dication, and 23 bonds and 18 angles of the Z-DNA nucleotides with dual conformation. The N atoms of the putrescine(2+) dication form three direct hydrogen bonds with the N7_G atoms of three different Z-DNA molecules, plus three water-mediated hydrogen bonds with cytosine, guanine and phosphate acceptors. A unique potassium cation was also unambiguously identified in the structure, albeit at a ∼0.5 occupation site shared with a water molecule, providing the first example of such a complex with Z-DNA. The K⁺ cation has coordination number of eight and an irregular coordination sphere, formed by four water molecules and four O atoms from two phosphate groups of the Z-DNA, including ligands present at fractional occupancy. The structural disorder of the Z-DNA duplex is manifested by the presence of alternate conformations along the DNA backbone. Comparison of the position and interactions of putrescine(2+) in the present structure with other ultra-high-resolution structures of Z-DNA in complexes with Mn²⁺ and Zn²⁺ ions shows that the dicationic putrescinium moiety can effectively substitute these metal ions for stabilization of Z-type DNA duplexes. Furthermore, this comparison also suggests that the spermine(4+) tetracation has a higher affinity for Z-DNA than K⁺.

SUBMITTER: Drozdzal P

PROVIDER: S-EPMC8182800 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

High-resolution crystal structure of Z-DNA in complex with Cr(3+) cations.

Project description:This work is part of our project aimed at characterizing metal-binding properties of left-handed Z-DNA helices. The three Cr(3+) cations found in the asymmetric unit of the d(CGCGCG)2-Cr(3+) crystal structure do not form direct coordination bonds with atoms of the Z-DNA molecule. Instead, the hydrated Cr(3+) ions are engaged in outer-sphere interactions with phosphate groups and O6 and N7 guanine atoms of the DNA. The Cr(3+)(1) and Cr(3+)(2) ions have disordered coordination spheres occupied by six water molecules each. These partial-occupancy chromium cations are 2.354(15) Å apart and are bridged by three water molecules from their hydration spheres. The Cr(3+)(3) cation has distorted square pyramidal geometry. In addition to the high degree of disorder of the DNA backbone, alternate conformations are also observed for the deoxyribose and base moieties of the G2 nucleotide. Our work illuminates the question of conformational flexibility of Z-DNA and its interaction mode with transition-metal cations.

| S-EPMC4381091 | biostudies-literature

High regularity of Z-DNA revealed by ultra high-resolution crystal structure at 0.55 A.

Project description:The crystal structure of a Z-DNA hexamer duplex d(CGCGCG)(2) determined at ultra high resolution of 0.55 Å and refined without restraints, displays a high degree of regularity and rigidity in its stereochemistry, in contrast to the more flexible B-DNA duplexes. The estimations of standard uncertainties of all individually refined parameters, obtained by full-matrix least-squares optimization, are comparable with values that are typical for small-molecule crystallography. The Z-DNA model generated with ultra high-resolution diffraction data can be used to revise the stereochemical restraints applied in lower resolution refinements. Detailed comparisons of the stereochemical library values with the present accurate Z-DNA parameters, shows in general a good agreement, but also reveals significant discrepancies in the description of guanine-sugar valence angles and in the geometry of the phosphate groups.

| S-EPMC3152349 | biostudies-literature

Crystal structure of the potassium-importing KdpFABC membrane complex.

Project description:Cellular potassium import systems play a fundamental role in osmoregulation, pH homeostasis and membrane potential in all domains of life. In bacteria, the kdp operon encodes a four-subunit potassium pump that maintains intracellular homeostasis, cell shape and turgor under conditions in which potassium is limiting. This membrane complex, called KdpFABC, has one channel-like subunit (KdpA) belonging to the superfamily of potassium transporters and another pump-like subunit (KdpB) belonging to the superfamily of P-type ATPases. Although there is considerable structural and functional information about members of both superfamilies, the mechanism by which uphill potassium transport through KdpA is coupled with ATP hydrolysis by KdpB remains poorly understood. Here we report the 2.9?Å X-ray structure of the complete Escherichia coli KdpFABC complex with a potassium ion within the selectivity filter of KdpA and a water molecule at a canonical cation site in the transmembrane domain of KdpB. The structure also reveals two structural elements that appear to mediate the coupling between these two subunits. Specifically, a protein-embedded tunnel runs between these potassium and water sites and a helix controlling the cytoplasmic gate of KdpA is linked to the phosphorylation domain of KdpB. On the basis of these observations, we propose a mechanism that repurposes protein channel architecture for active transport across biomembranes.

| S-EPMC5495170 | biostudies-literature

Crystal structure of MunI restriction endonuclease in complex with cognate DNA at 1.7 A resolution.

Project description:The MunI restriction enzyme recognizes the palindromic hexanucleotide sequence C/AATTG (the '/' indicates the cleavage site). The crystal structure of its active site mutant D83A bound to cognate DNA has been determined at 1.7 A resolution. Base-specific contacts between MunI and DNA occur exclusively in the major groove. While DNA-binding sites of most other restriction enzymes are comprised of discontinuous sequence segments, MunI combines all residues involved in the base-specific contacts within one short stretch (residues R115-R121) located at the N-terminal region of the 3(10)4 helix. The outer CG base pair of the recognition sequence is recognized solely by R115 through hydrogen bonds made by backbone and side chain atoms to both bases. The mechanism of recognition of the central AATT nucleotides by MunI is similar to that of EcoRI, which recognizes the G/AATTC sequence. The local conformation of AATT deviates from the typical B-DNA form and is remarkably similar to EcoRI-DNA. It appears to be essential for specific hydrogen bonding and recognition by MunI and EcoRI.

| S-EPMC1171646 | biostudies-other

Crystal structure of a putrescine aminotransferase from Pseudomonas sp. strain AAC.

Project description:The putrescine aminotransferase KES24511 from Pseudomonas sp. strain AAC was previously identified as an industrially relevant enzyme based on the discovery that it is able to promiscuously catalyse the transamination of 12-aminododecanoic acid. Here, the cloning, heterologous expression, purification and successful crystallization of the KES24511 protein are reported, which ultimately generated crystals adopting space group I2. The crystals diffracted X-rays to 2.07 Å resolution and data were collected using the microfocus beamline of the Australian Synchrotron. The structure was solved using molecular replacement, with a monomer from PDB entry 4a6t as the search model.

| S-EPMC5287375 | biostudies-literature

Crystal Structure of FOXC2 in Complex with DNA Target.

Project description:Forkhead transcription factor C2 (FOXC2) is a transcription factor regulating vascular and lymphatic development, and its mutations are linked to lymphedema-distichiasis syndrome. FOXC2 is also a crucial regulator of the epithelial-mesenchymal transition processes essential for tumor metastasis. Here, we report the crystal structure of the FOXC2-DNA-binding domain in complex with its cognate DNA. The crystal structure provides the basis of DNA sequence recognition by FOXC2 for the T/CAAAC motif. Helix 3 makes the majority of the DNA-protein interactions and confers the DNA sequence specificity. The computational energy calculation results also validate the structural observations. The FOXC2 and DNA complex structure provides a detailed picture of protein and DNA interactions, which allows us to predict its DNA recognition specificity and impaired functions in mutants identified in human patients.

| S-EPMC6648891 | biostudies-literature

Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution.

Project description:The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was determined at 2.6-A resolution. The overall fold of the molecule is that of an alpha(6)/alpha(6) barrel. It is a two-domain protein, and the Cbl is bound at the interface of the domains in a base-on conformation. Surprisingly, two full-length molecules, each comprising an alpha- and a beta-domain and one Cbl, and two truncated molecules with only an alpha- domain are present in the same asymmetric unit. The environment around Cbl is dominated by uncharged residues, and the sixth coordinate position of Co(2+) is empty. A detailed comparison between the IF-B12 complex and another Cbl transport protein complex, trans-Cbl-B12, has been made. The pH effect on the binding of Cbl analogues in transport proteins is analyzed. A possible basis for the lack of interchangeability of human and rat IF receptors is presented.

| S-EPMC2077253 | biostudies-literature

The high-resolution crystal structure of a parallel intermolecular DNA G-4 quadruplex/drug complex employing syn glycosyl linkages.

Project description:We have determined the X-ray structure of the complex between the DNA quadruplex d(5'-GGGG-3')(4) and daunomycin, as a potential model for studying drug-telomere interactions. The structure was solved at 1.08 Å by direct methods in space group I4. The asymmetric unit comprises a linear arrangement of one d(GGGG) strand, four daunomycin molecules, a second d(GGGG) strand facing in the opposite direction to the first, and Na and Mg cations. The crystallographic 4-fold axis generates the biological unit, which is a 12-layered structure comprising two sets of four guanine layers, with four layers each of four daunomycins stacked between the 5' faces of the two quadruplexes. The daunomycin layers fall into two groups which are novel in their mode of self assembly. The only contacts between daunomycin molecules within any one of these layers are van der Waals interactions, however there is substantial π-π stacking between successive daunomycin layers and also with adjacent guanine layers. The structure differs significantly from all other parallel d(TGGGGT)(4) quadruplexes in that the 5' guanine adopts the unusual syn glycosyl linkage, refuting the widespread belief that such conformations should all be anti. In contrast to the related d(TGGGGT)/daunomycin complex, there are no ligand-quadruplex groove insertion interactions.

| S-EPMC3384316 | biostudies-literature

Structure-guided DNA-DNA attraction mediated by divalent cations.

Project description:Probing the role of surface structure in electrostatic interactions, we report the first observation of sequence-dependent dsDNA condensation by divalent alkaline earth metal cations. Disparate behaviors were found between two repeating sequences with 100% AT content, a poly(A)-poly(T) duplex (AA-TT) and a poly(AT)-poly(TA) duplex (AT-TA). While AT-TA exhibits non-distinguishable behaviors from random-sequence genomic DNA, AA-TT condenses in all alkaline earth metal ions. We characterized these interactions experimentally and investigated the underlying principles using computer simulations. Both experiments and simulations demonstrate that AA-TT condensation is driven by non-specific ion-DNA interactions. Detailed analyses reveal sequence-enhanced major groove binding (SEGB) of point-charged alkali ions as the major difference between AA-TT and AT-TA, which originates from the continuous and close stacking of nucleobase partial charges. These SEGB cations elicit attraction via spatial juxtaposition with the phosphate backbone of neighboring helices, resulting in an azimuthal angular shift between apposing helices. Our study thus presents a distinct mechanism in which, sequence-directed surface motifs act with cations non-specifically to enact sequence-dependent behaviors. This physical insight allows a renewed understanding of the role of repeating sequences in genome organization and regulation and offers a facile approach for DNA technology to control the assembly process of nanostructures.

| S-EPMC7367160 | biostudies-literature

Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.

Project description:The steroid hormone receptors regulate important physiological functions such as reproduction, metabolism, immunity, and electrolyte balance. Mutations within steroid receptors result in endocrine disorders and can often drive cancer formation and progression. Despite the conserved three-dimensional structure shared among members of the steroid receptor family and their overlapping DNA binding preference, activation of individual steroid receptors drive unique effects on gene expression. Here, we present the first structure of the human mineralocorticoid receptor DNA binding domain, in complex with a canonical DNA response element. The overall structure is similar to the glucocorticoid receptor DNA binding domain, but small changes in the mode of DNA binding and lever arm conformation may begin to explain the differential effects on gene regulation by the mineralocorticoid and glucocorticoid receptors. In addition, we explore the structural effects of mineralocorticoid receptor DNA binding domain mutations found in type I pseudohypoaldosteronism and multiple types of cancer.

| S-EPMC4154765 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data