The absolute configuration of echitamine iodide by the X-ray technique

The absolute configuration of echitamine iodide has been determined by the Bijvoet technique, making use of the intensity differences between hkl and {Mathematical expression} reflections due to the anomalous scattering of CuKa radiation by the iodine atom. The various steps in the procedure are discussed in detail in this paper.

Cloning, expression, purification, crystallization and preliminary X-ray crystallographic study of the putative SAICAR synthetase (PH0239) from Pyrococcus horikoshii OT3

The study of proteins involved in de novo biosynthesis of purine nucleotides is central in the development of antibiotics and anticancer drugs. In view of this, a protein from the hyperthermophile Pyrococcus horikoshii OT3 was isolated, purified and crystallized using the microbatch method. Its primary structure was found to be similar to that of SAICAR synthetase, which catalyses the seventh step of de novo purine biosynthesis. A diffraction-quality crystal was obtained using Hampton Research Crystal Screen II condition No. 34, consisting of 0.05 M cadmium sulfate hydrate, 0.1 M HEPES buffer pH 7.5 and 1.0 M sodium acetate trihydrate, with 40%(v/v) 1,4-butanediol as an additive. The crystal belonged to space group P3(1), with unit-cell parameters a = b = 95.62, c = 149.13 angstrom. Assuming the presence of a hexamer in the asymmetric unit resulted in a Matthews coefficient (V-M) of 2.3 angstrom(3) Da(-1), corresponding to a solvent content of about 46%. A detailed study of this protein will yield insights into structural stability at high temperatures and should be highly relevant to the development of antibiotics and anticancer drugs targeting the biosynthesis of purine nucleotides.

Enhanced Ion Anisotropy by Nonconventional Coordination Geometry: Single-Chain Magnet Behavior for a [{(FeL)-L-II}(2){Nb-IV(CN)(8)}] Helical Chain Compound Designed with Heptacoordinate Fe-II

Nonconventional heptacoordination in combination with efficient magnetic exchange coupling is shown to yield a 1-D heteronuclear {(FeNbIV)-Nb-II} compound with remarkable magnetic features when compared to other Fe(II)-based single chain magnets (SCM). Cyano-bridged heterometallic {3d-4d} and {3d-5d} chains are formed upon assembling Fe(II) bearing a pentadentate macrocycle as the blocking ligand with octacyano metallates, [M(CN)(8)](4-) (M = Nb-IV, Mo-IV, W-IV.) X-ray diffraction (single-crystal and powder) measurements reveal that the [{(H2O)Fe(L-1)}{M(CN)(8)}{Fe(L-1)}](infinity) architectures consist of isomorphous 1-D polymeric structures based on the alternation of {Fe(L-1)}(2+) and {M(CN)(8)}(4-) units (L-1 stands for the pentadentate macrocycle). Analysis of the magnetic susceptibility behavior revealed cyano-bridged {Fe-Nb} exchange interaction to be antiferromagnetic with J = -20 cm(-1) deduced from fitting an Ising model taking into account the noncollinear spin arrangement. For this ferrimagnetic chain a slow relaxation of its magnetization is observed at low temperature revealing a SCM behavior with Delta/k(B) = 74 K and tau(0) = 4.6 x 10(-11) s. The M versus H behavior exhibits a hysteresis loop with a coercive field of 4 kOe at 1 K and reveals at 380 mK magnetic avalanche processes, i.e., abrupt reversals in magnetization as H is varied. The origin of these characteristics is attributed to the combination of efficient {Fe-Nb} exchange interaction and significant anisotropy of the {Fe(L-1)) unit. High field EPR and magnetization experiments have revealed for the parent compound [Fe(L-1)(H2O)(2)]Cl-2 a negative zero field splitting parameter of D approximate to -17 cm(-1). The crystal structure, magnetic behavior, and Mossbauer data for [Fe(L-1)(H2O)(2)]Cl-2 are also reported.

Enhanced Ion Anisotropy by Nonconventional Coordination Geometry: Single-Chain Magnet Behavior for a [{(FeL)-L-II}(2){Nb-IV(CN)(8)}] Helical Chain Compound Designed with Heptacoordinate Fe-II

Nonconventional heptacoordination in combination with efficient magnetic exchange coupling is shown to yield a 1-D heteronuclear {(FeNbIV)-Nb-II} compound with remarkable magnetic features when compared to other Fe(II)-based single chain magnets (SCM). Cyano-bridged heterometallic {3d-4d} and {3d-5d} chains are formed upon assembling Fe(II) bearing a pentadentate macrocycle as the blocking ligand with octacyano metallates, [M(CN)(8)](4-) (M = Nb-IV, Mo-IV, W-IV.) X-ray diffraction (single-crystal and powder) measurements reveal that the [{(H2O)Fe(L-1)}{M(CN)(8)}{Fe(L-1)}](infinity) architectures consist of isomorphous 1-D polymeric structures based on the alternation of {Fe(L-1)}(2+) and {M(CN)(8)}(4-) units (L-1 stands for the pentadentate macrocycle). Analysis of the magnetic susceptibility behavior revealed cyano-bridged {Fe-Nb} exchange interaction to be antiferromagnetic with J = -20 cm(-1) deduced from fitting an Ising model taking into account the noncollinear spin arrangement. For this ferrimagnetic chain a slow relaxation of its magnetization is observed at low temperature revealing a SCM behavior with Delta/k(B) = 74 K and tau(0) = 4.6 x 10(-11) s. The M versus H behavior exhibits a hysteresis loop with a coercive field of 4 kOe at 1 K and reveals at 380 mK magnetic avalanche processes, i.e., abrupt reversals in magnetization as H is varied. The origin of these characteristics is attributed to the combination of efficient {Fe-Nb} exchange interaction and significant anisotropy of the {Fe(L-1)) unit. High field EPR and magnetization experiments have revealed for the parent compound [Fe(L-1)(H2O)(2)]Cl-2 a negative zero field splitting parameter of D approximate to -17 cm(-1). The crystal structure, magnetic behavior, and Mossbauer data for [Fe(L-1)(H2O)(2)]Cl-2 are also reported.

X-ray Crystallographic Analysis of the Complexes of Enoyl Acyl Carrier Protein Reductase of Plasmodium falciparum with Triclosan Variants to Elucidate the Importance of Different Functional Groups in Enzyme Inhibition

Triclosan, a well-known inhibitor of Enoyl Acyl Carrier Protein Reductase (ENR) from several pathogenic organisms, is a promising lead compound to design effective drugs. We have solved the X-ray crystal structures of Plasmodium falciparum ENR in complex with triclosan variants having different substituted and unsubstituted groups at different key functional locations. The structures revealed that 4 and 2' substituted compounds have more interactions with the protein, cofactor, and solvents when compared with triclosan. New water molecules were found to interact with some of these inhibitors. Substitution at the 2' position of triclosan caused the relocation of a conserved water molecule, leading to an additional hydrogen bond with the inhibitor. This observation can help in conserved water-based inhibitor design. 2' and 4' unsubstituted compounds showed a movement away from the hydrophobic pocket to compensate for the interactions made by the halogen groups of triclosan. This compound also makes additional interactions with the protein and cofactor which compensate for the lost interactions due to the unsubstitution at 2' and 4'. In cell culture, this inhibitor shows less potency, which indicates that the chlorines at 2' and 4' positions increase the ability of the inhibitor to cross multilayered membranes. This knowledge helps us to modify the different functional groups of triclosan to get more potent inhibitors. (C) 2010 IUBMB IUBMB Life, 62(6): 467-476.

Structures of apo and GTP-bound molybdenum cofactor biosynthesis protein MoaC from Thermus thermophilus HB8

The first step in the molybdenum cofactor (Moco) biosynthesis pathway involves the conversion of guanosine triphosphate (GTP) to precursor Z by two proteins (MoaA and MoaC). MoaA belongs to the S-adenosylmethioninedependent radical enzyme superfamily and is believed to generate protein and/or substrate radicals by reductive cleavage of S-adenosylmethionine using an Fe-S cluster. MoaC has been suggested to catalyze the release of pyrophosphate and the formation of the cyclic phosphate of precursor Z. However, structural evidence showing the binding of a substrate-like molecule to MoaC is not available. Here, apo and GTP-bound crystal structures of MoaC from Thermus thermophilus HB8 are reported. Furthermore, isothermal titration calorimetry experiments have been carried out in order to obtain thermodynamic parameters for the protein-ligand interactions. In addition, molecular-dynamics (MD) simulations have been carried out on the protein-ligand complex of known structure and on models of relevant complexes for which X-ray structures are not available. The biophysical, structural and MD results reveal the residues that are involved in substrate binding and help in speculating upon a possible mechanism.

X-ray photoelectron spectroscopy of superconducting RuSr2Eu1.5Ce0.5Cu2O10 and nonsuperconducting RuSr2EuCeCu2O10

We report x-ray photoelectron spectroscopic investigation of RuSr2Eu1.5Ce0.5Cu2O10 with ferromagnetic T-C similar to 100 K and a superconducting transition temperature of similar to 30 K compared with RuSr2EuCeCu2O10, which is a ferromagnetic (T-C similar to 150 K) insulator. Our results show that the rare earths, Eu and Ce, are in 3+ and 4+ states, respectively. Comparing the Ru core level spectra from these compounds to those from two Ru reference oxides, we also show that Ru in these ruthenocuprates is always in 5+ state, suggesting that the doped holes in the superconducting compound arising from the substitution of Ce4+ by Eu3+ are primarily in the Cu-O plane, in close analogy to all other doped high-T-C cuprates. Analysis of Cu 2p spectra in terms of a configuration interaction model provides a quantitative description of the gross electronic structures of these ruthenocuprates.