Auto-hydroxylation of FIH-1: an Fe(ii), alpha-ketoglutarate-dependent human hypoxia sensor

HIF-asparaginyl hydroxylase (FIH-1) normally couples O(2)-activation to hydroxylation of Asn(803) on the alpha-subunit of the hypoxia-inducible factor (HIFalpha), a key step in pO(2) sensing; in the absence of HIFalpha, O(2)-activation becomes uncoupled, leading to self-hydroxylation at Trp(296) and a purple Fe(iii)-O-Trp chromophore-this alternative reactivity may affect human hypoxia sensing.     

Turn-on fluorescence detection of H2O2 and TATP

Peroxide-based explosives, like triacetone triperoxide (TATP), are important targets for detection because of their broad use in improvised explosives but pose challenges. We report a highly sensitive turn-on fluorescence detection for H2O2 and organic peroxides, including TATP. The detection strategy relies on oxidative deboronation to unmask H2Salen, which subsequently binds Zn(2+) to form fluorescent Zn(Salen). Sensitivity is excellent, with detection limits below 10 nM for H2O2, TATP, and benzoyl peroxide. In addition, acid treatment is necessary to sense TATP, suggesting the potential to discriminate between H2O2 and TATP based upon minimal sample pretreatment.     

Tautomeric modification of GlcNAc-thiazoline

The potent O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline has been modified by buffer- or acylation-induced imine-to-enamine conversion and then electrophile or radical addition (Xn = D3, F, N3, OH, SMe, COCF3, CF3). Several functionalized GlcNAc-thiazolines show highly selective inhibition of OGA vs human hexosaminidase and thus have promise as tools for targeted investigations of OGA, an enzyme linked to diabetes and neurodegeneration. A new radical addition/fragmentation reaction of the N-(trifluoroacetyl)enamine has been discovered.     

Protonation states of ammonia/ammonium in the hydrophobic pore of ammonia transporter protein AmtB

The crystal structure of the ammonia transport (Amt) protein AmtB at 1.4 Angstrom resolution revealed four ammonia/ammonium (NH(3)/NH(4)(+)) binding sites along the approximately 20 Angstrom narrow pore. It is an open question whether the bound NH(3)/NH(4)(+) are neutral (NH(3)) or cationic (NH(4)(+)). On the basis of the AmtB crystal structure, we calculated the pK(a) of these four NH(3)/NH(4)(+) by solving the Poisson-Boltzmann equation. Except for one NH(3)/NH(4)(+) binding site (Am1) at the entry point of the Amt pore, binding sites are occupied by NH(3) due to lack of energy contributions from solvation, eliminating an existence of charged form NH(4)(+) and, inevitably, its potential cation-pi interaction. The only two titratable residues in the pore, His168 and His318, are in the neutral charge state. The NH(4)(+) charge state at the Am1 site is stabilized by Ser219 functioning as an H-bond acceptor. However, when involving explicit crystal water nearby, the NH(3) charge state is stabilized by the reorientation of Ser219-OH group. This H-bond donor Ser219 significantly decreases the pK(a) of NH(3)/ NH(4)(+) at the Am1 site to approximately 1. The flip/flop H-bond of Ser219 may play a dual role first in binding and subsequently in deprotonating NH(4)(+), which is a prerequisite to conduct NH(3) through the Amt pore across the membrane.     

Recognition and modulation of cytochrome c's redox properties using an amphiphilic homopolymer

An amphiphilic homopolymer scaffold has been used to bind to the protein, cytochrome c. This interaction is analyzed using cyclic voltammetry, native gel electrophoresis, UV-visible absorption, and circular dichroism spectroscopy. The polymer binds to cytochrome c with micromolar affinity and the association of polymer with cytochrome c leads to a structural change of the protein. This conformational change exposes the heme unit of the protein, which affords an opportunity to reversibly modulate its electron-transfer properties. We have also shown that the electrostatic binding of polymer to cytochrome c can be used to disrupt its interaction with its natural partner, cytochrome c peroxidase.     

Limits of discrete series with infinitesimal character zero

For a connected linear semisimple Lie group , this paper considers those nonzero limits of discrete series representations having infinitesimal character 0, calling them totally degenerate. Such representations exist if and only if has a compact Cartan subgroup, is quasisplit, and is acceptable in the sense of Harish-Chandra.

Totally degenerate limits of discrete series are natural objects of study in the theory of automorphic forms: in fact, those automorphic representations of adelic groups that have totally degenerate limits of discrete series as archimedean components correspond conjecturally to complex continuous representations of Galois groups of number fields. The automorphic representations in question have important arithmetic significance, but very little has been proved up to now toward establishing this part of the Langlands conjectures.

There is some hope of making progress in this area, and for that one needs to know in detail the representations of under consideration. The aim of this paper is to determine the classification parameters of all totally degenerate limits of discrete series in the Knapp-Zuckerman classification of irreducible tempered representations, i.e., to express these representations as induced representations with nondegenerate data.

The paper uses a general argument, based on the finite abelian reducibility group attached to a specific unitary principal series representation of . First an easy result gives the aggregate of the classification parameters. Then a harder result uses the easy result to match the classification parameters with the representations of under consideration in representation-by-representation fashion. The paper includes tables of the classification parameters for all such groups .

     

Reaction mechanism of ammonia oxidation over RuO2(1 1 0): A combined theory/experiment approach

Combining state-of-the-art density functional theory (DFT) calculations with high resolution core level shift spectroscopy experiments we explored the reaction mechanism of the ammonia oxidation reaction over RuO₂(1 1 0). The high catalytic activity of RuO₂(1 1 0) is traced to the low activation energies for the successive hydrogen abstractions of ammonia by on-top O (less than 73 kJ/mol) and the low activation barrier for the recombination of adsorbed O and N (77 kJ/mol) to form adsorbed NO. The NO desorption is activated by 121 kJ/mol and represents therefore the rate determining step in the ammonia oxidation reaction over RuO₂ (1 1 0).