Michiko Konno

Modeling of tRNA‐assisted mechanism of Arg activation based on a structure of Arg‐tRNA synthetase, tRNA, and an ATP analog (ANP)

The ATP–pyrophosphate exchange reaction catalyzed by Arg‐tRNA, Gln‐tRNA and Glu‐tRNA synthetases requires the assistance of the cognate tRNA. tRNA also assists Arg‐tRNA synthetase in catalyzing the pyrophosphorolysis of synthetic Arg‐AMP at low pH. The mechanism by which the 3′‐end A76, and in particular its hydroxyl group, of the cognate tRNA is involved with the exchange reaction catalyzed by those enzymes has yet to be established. We determined a crystal structure of a complex of Arg‐tRNA synthetase from Pyrococcus horikoshii, tRNAArgCCU and an ATP analog with Rfactor = 0.213 (Rfree = 0.253) at 2.0 Å resolution. On the basis of newly obtained structural information about the position of ATP bound on the enzyme, we constructed a structural model for a mechanism in which the formation of a hydrogen bond between the 2′‐OH group of A76 of tRNA and the carboxyl group of Arg induces both formation of Arg‐AMP (Arg + ATP → Arg‐AMP + pyrophosphate) and pyrophosphorolysis of Arg‐AMP (Arg‐AMP + pyrophosphate → Arg + ATP) at low pH. Furthermore, we obtained a structural model of the molecular mechanism for the Arg‐tRNA synthetase‐catalyzed deacylation of Arg‐tRNA (Arg‐tRNA + AMP → Arg‐AMP + tRNA at high pH), in which the deacylation of aminoacyl‐tRNA bound on Arg‐tRNA synthetase and Glu‐tRNA synthetase is catalyzed by a quite similar mechanism, whereby the proton‐donating group (–NH–C+(NH2)2 or –COOH) of Arg and Glu assists the aminoacyl transfer from the 2′‐OH group of tRNA to the phosphate group of AMP at high pH.

Crystal structure of non-allosteric L-lactate dehydrogenase from Lactobacillus pentosus at 2.3 Å resolution: Specific interactions at subunit interfaces †

L‐Lactate dehydrogenase (LDH) from Lactobacillus pentosus is a non‐allosteric enzyme, which shows, however, high sequence similarity to allosteric LDHs from certain bacteria. To elucidate the structural basis of the absence of allostery of L. pentosus LDH (LPLDH), we determined the crystal structure of LPLDH at 2.3 Å resolution. Bacterial LDHs are tetrameric enzymes composed of identical subunits and exhibit 222 symmetry. The quaternary structure of LPLDH was similar to the active conformation of allosteric LDHs. Structural analysis revealed that the subunit interfaces of LPLDH are optimized mainly through hydrophilic interactions rather than hydrophobic interactions, compared with other LDHs. The subunit interfaces of LPLDH are more specifically stabilized by increased numbers of intersubunit salt bridges and hydrogen bonds, and higher geometrical complementarity. Such high specificity at the subunit interfaces should hinder the rearrangement of the quaternary structure needed for allosteric regulation and thus explain the “non‐allostery” of LPLDH. Proteins 2002;46:206–214.

Novel structural and electronic properties of (MDT-TTF)2Au(CN)2

Abstract The novel structural and electronic properties of a new organic metal (MDT-TTF)2Au(CN)2 were studied (MDT-TTF = methylendithiotetrathiafulvalene). Experimental evidence for the occurence of an SDW state was confirmed below 20 K by the electrical resistivity, EPR and 1H-NMR measurements, though the structural and electrical investigations suggest substantial two-dimensional nature of this compound. The SDW state is easily suppressed by an application of pressure.

Electrical and optical properties and crystal structure of bis (dimethylglyoximato)Pt(II) at high pressures

Abstract The electrical resistivity, the electronic and infrared spectra, and the crystal structure in bis(dimethylglyoximato)Pt(II), Pt(dmg)2, have been studied at high pressures. The electrical resistivity in the single crystal was measured under quasi-hydrostatic condition. The resistivity drastically decreased with increasing pressure; the metallic behavior was observed at around 4.6 GPa. Pt(dmg)2 behaved again as a semiconductor above about 6 GPa. A new absorption band was found above 6 GPa. The intensity of the absorption band was abruptly increased with pressure over a narrow pressure range of 6 to 8 Gpa. The crystal structure of the complex was studied at high pressures. X-ray work for a single crystal was carried out by the use of the diamond-anvil cell developed by Merrill and Bassett. The lattice constants of three axes decreased rapidly with pressure; the b lattice constant was not sensitive to pressure above 1.5 GPa. Strong intermolecular contacts of O—HC type was observed between adjacent chains along the b axis at high pressure. The relation between the structure and the electrical and optical properties at high pressure is discussed.

A prediction system of oxidation reaction as a solid-state stress condition: Applied to a pyrrole-containing pharmaceutical compound

Stress conditions for predicting oxidative degradation products in solid-state pharmaceutical compounds were investigated. 4-Methyl-2-(3,4-dimethylphenyl)-1-(4-sulfamoylphenyl)pyrrole, Compound A, was used as the model compound for this study and its four main degradation products were due to oxidation, as identified by LC-MS and LC-(1)H NMR. In order to develop a prediction system for the oxidation reaction, solid-state Compound A was stored under moisture-saturated conditions. Hydrogen peroxide was added to the solution used to saturate the headspace with moisture and oxygen was substituted for the headspace air, in order to stimulate the oxidation reaction. After optimizing the conditions, a similar degradation product profile to that actually observed in the stability studies was obtained in only 3 days under conditions using 3% hydrogen peroxide at 40 degrees C. The prediction of the oxidative degradation products in a solid-state pharmaceutical compound was successfully achieved in a short term utilizing this newly developed prediction system.

Parameter landscape analysis for common motif discovery programs

The identification of regulatory elements as over-represented motifs in the promoters of potentially co-regulated genes is an important and challenging problem in computational biology. Although many motif detection programs have been developed so far, they still seem to be immature practically. In particular the choice of tunable parameters is often critical to success. Thus knowledge regarding which parameter settings are most appropriate for various types of target motifs is invaluable, but unfortunately has been scarce. In this paper, we report our parameter landscape analysis of two widely-used programs (the Gibbs Sampler (GS) and MEME). Our results show that GS is relatively sensitive to the changes of some parameter values while MEME is more stable. We present recommended parameter settings for GS optimized for four different motif lengths. Thus, running GS four times with these settings should significantly decrease the risk of overlooking subtle motifs.

Valence-delocalization of the mixed-valence oxo-centered trinuclear iron propionates [Fe 2 III FeIIO(C2H5CO2)6(py)3]npy;n=0, 1.5

Mixed-valence trinuclear iron propionates [Fe2IIIFeIIO(C2H5CO2)6(py)3]npy, wheren=0, 1.5, were synthesized and the structure of the pyridine-solvated complex was determined by single-crystal X-ray diffraction. Mössbauer spectra of the solvated propionate complex showed a temperature-dependent mixed-valence state related to phase transitions, reaching an almost delocalized valence state at room temperature. On the other hand, the non-solvated propionate showed a remarkable change of the spectral shape related to a phase transition, remaining in a localized valence state at higher temperatures up to room temperature.

Crystal structure and mixed-valence state in 1′,1‴-dibutylbiferrocenium triiodide

In 1′, 1‴-dibutylbiferrocenium triiodide crystals A show temperature-independent trapped-valence state, while crystals B show a valence-delocalization of the mixed-valence state. The mixed-valence states of both crystals are discussed in relation to their crystal structures.

C1TET-TTF and its Related Compounds as Single Component Molecular Conductors

Abstract Bis(methylthio)ethylenedithio-TTF (C1TET-TTF) single crystals showed the room temperature resistivity of 5.4×105 ωcm. X-Ray crystal determination indicates that boat shaped molecules of C1TET-TTF construct two-dimensional network of the intermolecular S··S atomic contacts. C10TET-TTF showed the value of 1.0×106 ωcm in compaction though only two alkyl chains are attached to its π-electron moiety.

New organic metals based on vinylenedithio-annulated diselenadithiafulvalene derivatives

The synthesis of vinylenedithio-annulated DSDTF (diselenadithiafulvalene) derivatives 1–3 and their radical cation salts are investigated, serveral of which exhibit metallic conducting behaviour.