Crystal structure of the co-crystalline adduct 1,3,6,8-tetra-aza-tri-cyclo-[22.214.171.124,8]dodecane (TATD)-4-iodo-phenol (1/2): supra-molecular assembly mediated by halogen and hydrogen bonding.
ABSTRACT: The asymmetric unit of the title co-crystalline adduct, 1,3,6,8-tetra-aza-tri-cyclo[126.96.36.199,8]dodecane (TATD)-4-iodo-phenol (1/2), C8H16N4·2C6H5IO, comprises a half mol-ecule of the aminal cage polyamine plus a 4-iodo-phenol mol-ecule. A twofold rotation axis generates the other half of the adduct. The components are linked by two inter-molecular O-H?N hydrogen bonds. The adducts are further linked into a three-dimensional framework structure by a combination of N?I halogen bonds and weak non-conventional C-H?O and C-H?I hydrogen bonds.
Project description:The structure of the 1:2 co-crystalline adduct C8H16N4·2C6H5BrO, (I), from the solid-state reaction of 1,3,6,8-tetra-aza-tri-cyclo-[188.8.131.52(3,8)]dodecane (TATD) and 4-bromo-phenol, has been determined. The asymmetric unit of the title co-crystalline adduct comprises a half mol-ecule of aminal cage polyamine plus a 4-bromo-phenol mol-ecule. A twofold rotation axis generates the other half of the adduct. The primary inter-species association in the title compound is through two inter-molecular O-H?N hydrogen bonds. In the crystal, the adducts are linked by weak non-conventional C-H?O and C-H?Br hydrogen bonds, giving a two-dimensional supra-molecular structure parallel to the bc plane.
Project description:In the crystal of the title co-crystalline adduct, C8H16N4·C8H9ClO, (I), prepared by solid-state reaction, the mol-ecules are linked by inter-molecular O-H?N hydrogen bonds, forming a D motif. The aza-adamantane structure in (I) is slightly distorted, with N-CH2-CH2-N torsion angles of 10.4?(3) and -9.0?(3)°. These values differ slightly from the corresponding torsion angles in the free aminal cage (0.0°) and in related co-crystalline adducts, which are not far from a planar geometry and consistent with a D 2d mol-ecular symmetry in the tetra-aza-tri-cyclo structure. The structures also differ in that there is a slight elongation of the N-C bond lengths about the N atom that accepts the hydrogen bond in (I) compared with the other N-C bond lengths. In the crystal, the two mol-ecules are not only linked by a classical O-H?N hydrogen bond but are further connected by weak C-H?? inter-actions, forming a two-dimensional supra-molecular network parallel to the bc plane.
Project description:Solvent-free treatment of 1,3,6,8-tetra-aza-tri-cyclo-[184.108.40.206,8]undecano (TATU) with 4-chloro-3,5-di-methyl-phenol led to the formation of the title co-crystal, C7H14N4·2C8H9ClO. The asymmetric unit contains one aminal cage mol-ecule and two phenol mol-ecules linked via two O-H?N hydrogen bonds. In the aminal cage, the N-CH2-CH2-N unit is slightly distorted from a syn periplanar geometry. Aromatic ?-? stacking between the benzene rings from two different neighbouring phenol mol-ecules [centroid-centroid distance = 4.0570?(11)?Å] consolidates the crystal packing.
Project description:In the title compound, C7H14N4·2C6H5ClO, which crystallized with two crystallographically independent 4-chloro-phenol mol-ecules and one 1,3,6,8-tetra-aza-tri-cyclo-[220.127.116.11,8]undecane (TATU) mol-ecule in the asymmetric unit, the independent components are linked by two O-H?N hydrogen bonds. The hydrogen-bond acceptor sites are two non-equivalent N atoms from the aminal cage structure, and the tricyclic system distorts by changing the C-N bond lengths. In the crystal, these hydrogen-bonded aggregates are linked into chains along the c axis by C-H?N hydrogen bonds. The crystal structure also features C-H?? contacts.
Project description:TatD is an evolutionarily conserved protein with thousands of homologues in all kingdoms of life. It has been suggested that TatD participates in DNA fragmentation during apoptosis in eukaryotic cells. However, the cellular functions and biochemical properties of TatD in bacterial and non-apoptotic eukaryotic cells remain elusive. Here we show that Escherichia coli TatD is a Mg(2+)-dependent 3'-5' exonuclease that prefers to digest single-stranded DNA and RNA. TatD-knockout cells are less resistant to the DNA damaging agent hydrogen peroxide, and TatD can remove damaged deaminated nucleotides from a DNA chain, suggesting that it may play a role in the H2O2-induced DNA repair. The crystal structure of the apo-form TatD and TatD bound to a single-stranded three-nucleotide DNA was determined by X-ray diffraction methods at a resolution of 2.0 and 2.9 Å, respectively. TatD has a TIM-barrel fold and the single-stranded DNA is bound at the loop region on the top of the barrel. Mutational studies further identify important conserved metal ion-binding and catalytic residues in the TatD active site for DNA hydrolysis. We thus conclude that TatD is a new class of TIM-barrel 3'-5' exonuclease that not only degrades chromosomal DNA during apoptosis but also processes single-stranded DNA during DNA repair.
Project description:The TatD-like DNase of <i>Plasmodium</i> species has previously been characterized as a conserved antigen that plays an important role in immune evasion. Here, we found that TatD-like DNase is expressed, apart from the erythrocytic stage, throughout the developmental stages of the parasite in the mosquito vector. Antibodies to the molecule significantly blocked parasites development and transition in the mosquito gut. Further, mice immunized with recombinant TatD-like DNase showed significant resistance to parasite challenge. The antigenicity of the TatD-like antigen in combination with various adjuvants, including Freund's adjuvants, Montanide ISA 51 and 61, Alhydrogel (aluminum hydroxide), and levamisole was investigated. It was found that immunization of the recombinant TatD-like DNase in combination with Montanide ISA 51 induced strong <b>humoral</b> responses that showed significant protection against parasite challenge in a mouse model. The data further support that TatD-like DNase is a functionally important molecule in the whole development cycle of the malaria parasites and a candidate for malaria vaccine development.
Project description:Neutrophil extracellular traps (NETs), composed primarily of DNA and proteases, are released from activated neutrophils and contribute to the innate immune response by capturing pathogens. Plasmodium falciparum, the causative agent of severe malaria, thrives in its host by counteracting immune elimination. Here, we report the discovery of a novel virulence factor of P. falciparum, a TatD-like DNase (PfTatD) that is expressed primarily in the asexual blood stage and is likely utilized by the parasite to counteract NETs. PfTatD exhibits typical deoxyribonuclease activity, and its expression is higher in virulent parasites than in avirulent parasites. A P. berghei TatD-knockout parasite displays reduced pathogenicity in mice. Mice immunized with recombinant TatD exhibit increased immunity against lethal challenge. Our results suggest that the TatD-like DNase is an essential factor for the survival of malarial parasites in the host and is a potential malaria vaccine candidate.
Project description:The title compound C(14)H(29)N(4) (+)·I(-) salt, was obtained by the reaction of cage adamanzane-type aminal 1,3,6,8-tetra-aza-tricyclo-[18.104.22.168(3,8)]undecane with heptyl iodide. In the cation, the bond lengths and angles are within normal ranges, except for one N-C(ring) bond distance of 1.542?(3)?Å, which is unexpectedly long compared with related compounds. In the crystal, ions are linked through C-H?I hydrogen bonds. The crystal studied was a non-merohedral twin with a minor twin domain of 6.56?(5)%.
Project description:TatD has been thoroughly investigated as a DNA-repair enzyme and an apoptotic nuclease, and still-unknown TatD-related DNases are considered to play crucial cellular roles. However, studies of TatD from Gram-positive bacteria have been hindered by an absence of atomic detail and the resulting inability to determine function from structure. In this study, an X-ray crystal structure of SAV0491, which is the TatD enzyme from the Gram-positive bacterium Staphylococcus aureus (SaTatD), is reported at a high resolution of 1.85?Å with a detailed atomic description. Although SaTatD has the common TIM-barrel fold shared by most TatD-related homologs, and PDB entry 2gzx shares 100% sequence identity with SAV0491, the crystal structure of SaTatD revealed a unique binding mode of two phosphates interacting with two Ni2+ ions. Through a functional study, it was verified that SaTatD has Mg2+-dependent nuclease activity as a DNase and an RNase. In addition, structural comparison with TatD homologs and the identification of key residues contributing to the binding mode of Ni2+ ions and phosphates allowed mutational studies to be performed that revealed the catalytic mechanism of SaTatD. Among the key residues composing the active site, the acidic residues Glu92 and Glu202 had a critical impact on catalysis by SaTatD. Furthermore, based on the binding mode of the two phosphates and structural insights, a putative DNA-binding mode of SaTatD was proposed using in silico docking. Overall, these findings may serve as a good basis for understanding the relationship between the structure and function of TatD proteins from Gram-positive bacteria and may provide critical insights into the DNA-binding mode of SaTatD.
Project description:In the title 1:1 adduct, C6H5NO3·C6H5NO2, both mol-ecules are almost planar (r.m.s. deviations for the non-H atoms = 0.027 and 0.023?Å for 4-nitro-phenol and 2-carboxyl-atopyridinium, respectively). The pyridine mol-ecule crystallizes as a zwitterion (nominal proton transfer from the carb-oxy-lic acid group to the N atom in the ring). In the crystal, inversion dimers of the zwitterions linked by pairs of N-H?O hydrogen bonds generate R 2 (2)(10) loops; two 4-nitro-phenol mol-ecules link to the dimer by O-H?O hydrogen bonds, generating a four-molecule aggregate. These are linked by C-H?O inter-actions, forming a three-dimensional network.