Physical constraints and functional plasticity of cellulases.

Enzyme reactions, both in Nature and technical applications, commonly occur at the interface of immiscible phases. Nevertheless, stringent descriptions of interfacial enzyme catalysis remain sparse, and this is partly due to a shortage of coherent experimental data to guide and assess such work. In this work, we produced and kinetically characterized 83 cellulases, which revealed a conspicuous linear free energy relationship (LFER) between the substrate binding strength and the activation barrier. The scaling occurred despite the investigated enzymes being structurally and mechanistically diverse. We suggest that the scaling reflects basic physical restrictions of the hydrolytic process and that evolutionary selection has condensed cellulase phenotypes near the line. One consequence of the LFER is that the activity of a cellulase can be estimated from its substrate binding strength, irrespectively of structural and mechanistic details, and this appears promising for in silico selection and design within this industrially important group of enzymes.

Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes.

BACKGROUND AND AIMS: Since hyperglycemia promotes inflammation by different pathways and inflammation participates in the development of chronic diabetes complications, we investigated the association between the leukotriene (LT) pathway and microvascular diabetes complications. METHODS AND RESULTS: Quantitative polymerase chain reaction was employed to quantify the expression of ALOX5 (encodes 5-lipoxygenase), LTB4R (encodes one of the LTB4 receptors), and MYD88 in peripheral blood mononuclear cells from 164 type 1 diabetes (T1D) individuals presenting or not diabetes kidney disease, retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN); 26 nondiabetic subjects were included as controls. LTB4 plasmatic concentrations were also evaluated. The expression of LTB4R was significantly higher in T1D individuals than in controls. T1D individuals with microvascular complications presented lower MYD88 mRNA expression when compared to those without microvascular complications. Higher LTB4 concentrations were found in individuals with CAN versus without CAN. The observation of two distinct subgroups of T1D individuals in the correlation analyses motivated us to evaluate the characteristics of each one of these groups separately. The group presenting higher expression of ALOX5 and of LTB4R also presented higher values of HbA1C, of fructosamine, and of plasmatic LTB4. CONCLUSION: In the diabetes setting, the LT pathway is not only activated by hyperglycemia but is also modulated by the status of the autonomic nervous system.

Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients.

Quantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE ( AGER) and AGER1 ( DDOST)] and of the gene coding the deacetylase SIRT1 ( SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming ≥12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.

Organic-inorganic hybrid materials based on iron(III)-polyoxotungstates and 1-butyl-3-methylimidazolium cations.

The iron(III) µ-oxo bridged dimeric polyoxometalate [(PW(11)O(39)Fe)(2)O](10-) was isolated by reacting the transition metal monosubstituted Keggin anion [PW(11)O(39)Fe(H(2)O)](4-) and the ionic liquid 1-butyl-3-methylimidazolium bromide, (Bmim)Br, at pH 5.5. The crystal structure of (Bmim)(10)[(PW(11)O(39)Fe)(2)O]·0.5H(2)O (1) (monoclinic, space group P2(1)/n, Z = 4) was determined by single crystal X-ray diffraction. By changing the reaction conditions, (Bmim)(4)[PW(11)O(39)Fe(H(2)O)]·H(2)O (2) was obtained, whilst the reaction between the Bmim(+) cation and the heteropolyanion [SiW(11)O(39)Fe(H(2)O](5-), in the pH conditions used for 1, afforded (Bmim)(5)[SiW(11)O(39)Fe(H(2)O)]·4H(2)O (3). The compounds were characterized by spectroscopic techniques, thermal analysis, cyclic voltammetry, magnetic measurements and mass spectrometry. This study contributes to the understanding of iron µ-oxo dimer formation in polyoxometalate chemistry and calls attention to the influence of the counter-cations on the stability and formation of compound 1. The combination of the cationic part of ionic liquids and iron-substituted polyoxotungstates is predicted to lead to new materials with interest to catalysis, electrocatalysis and ionic liquid based nanocomposites.

Novel cerium(IV) heteropolyoxotungstate containing two types of lacunary Keggin anions.

A novel V-shaped polyoxotungstate is formed when Ce(IV) metal centres bridge monolacunary [PW(11)O(39)](7-) anions to an unusual 1,4-bilacunary [PW(10)O(38)](11-) anion which appears with an unprecedented bridging structural motif.

Lanthanopolyoxotungstoborates: synthesis, characterization, and layer-by-layer assembly of europium photoluminescent nanostructured films.

New lanthanopolyoxotungstoborates, K6-xHx[Ln(BW11O39)(H2O)3].nH2O, Ln(III) = Sm, Eu, Tb, Er, were prepared and characterized by spectroscopic methods (Fourier transform infrared, Fourier transform-Raman, 11B solid-state nuclear magnetic resonance, and photoluminescence) and elemental analysis. A layer-by-layer assembly method was employed to fabricate multilayered films containing the europium heteropolyanion and the polyelectrolytes poly(sodium 4-styrenesulfonate) and poly(diallydimethylammonium chloride). The photoluminescence behavior of these final nanostructures was investigated and compared with that of the starting Eu(III) polyoxometalate used as the building unit.