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141.
142.
The substitution of Ser187, a residue located far from the active site of human liver peroxisomal alanine:glyoxylate aminotransferase (AGT), by Phe gives rise to a variant associated with primary hyperoxaluria type I. Unexpectedly, previous studies revealed that the recombinant form of S187F exhibits a remarkable loss of catalytic activity, an increased pyridoxal 5′‐phosphate (PLP) binding affinity and a different coenzyme binding mode compared with normal AGT. To shed light on the structural elements responsible for these defects, we solved the crystal structure of the variant to a resolution of 2.9 Å. Although the overall conformation of the variant is similar to that of normal AGT, we noticed: (i) a displacement of the PLP‐binding Lys209 and Val185, located on the re and si side of PLP, respectively, and (ii) slight conformational changes of other active site residues, in particular Trp108, the base stacking residue with the pyridine cofactor moiety. This active site perturbation results in a mispositioning of the AGT‐pyridoxamine 5′‐phosphate (PMP) complex and of the external aldimine, as predicted by molecular modeling studies. Taken together, both predicted and observed movements caused by the S187F mutation are consistent with the following functional properties of the variant: (i) a 300‐ to 500‐fold decrease in both the rate constant of L‐alanine half‐transamination and the kcat of the overall transamination, (ii) a different PMP binding mode and affinity, and (iii) a different microenvironment of the external aldimine. Proposals for the treatment of patients bearing S187F mutation are discussed on the basis of these results. Proteins 2013; 81:1457–1465. © 2013 Wiley Periodicals, Inc. 相似文献
143.
Rena Li Ping He Jie Cui Matthias Staufenbiel Nobuhiro Harada Yong Shen 《Molecular neurobiology》2013,47(3):857-867
Estrogens have been found to improve memory and reduce risk of dementia, although conflicting results such as failure of estrogen replacement therapy for treatment of Alzheimer's disease (AD) also has been reported. Only recently, our published human brain studies showed a depletion of brain estrogen in women with AD, while other studies have demonstrated cognitive impairment believed to be caused by inhibition of endogenous estrogen synthesis in females. To investigate whether the shortage of brain estrogen alters the sensitivity of response to estrogen replacement therapy, we have used genetic and surgical animal models to examine the response of estrogen treatment in AD neuropathology. Our studies have shown that early treatment with 17β-estradiol (E2) or genistein could reduce brain amyloid levels by increasing Aβ clearance in both APP23 mice with genetic deficiency of aromatase (APP/Ar+/?), in which the brains contain nondetectable levels of estrogen, and in APP23 mice with an ovariectomy (APP/OVX), in which the brains still contain certain levels of estrogen. However, only APP/Ar+/? mice showed a great reduction in brain amyloid plaque formation after E2 or genistein treatment along with downregulation of β-secretase (BACE1) mRNA and protein expression. Our results suggest that early and long-term usage of E2 and/or genistein may prevent AD pathologies in a dependent manner on endogenous brain estrogen levels in aged females. 相似文献
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145.
Ronald K. Mulwa Eike Lena Neuschulz Katrin Böhning‐Gaese Matthias Schleuning 《Oikos》2013,122(4):524-532
Seasonal fluctuations in climatic factors are expected to increase in future decades. However, little is known about the response of tropical species communities to seasonal fluctuations in climate and resource availability, particularly across different habitat types. We examined the relationship between spatio‐temporal fluctuations in the abundance of fruits and invertebrates and two avian feeding guilds, i.e. frugivores and insectivores, in forest and farmland habitats in western Kenya. Fruits and invertebrates fluctuated substantially throughout the year, but seasonal fluctuations were asynchronous between the two habitat types. Species richness and total abundance of frugivores and insectivores also fluctuated strongly and were closely related to the abundance of their respective resources. Frugivore species richness fluctuated anti‐cyclical in forest and farmland habitats, suggesting that several frugivorous species tracked fruit resources across habitat boundaries. In contrast, insectivorous bird richness fluctuated synchronously in the two habitat types, suggesting a lack of local‐scale movements across habitat boundaries. We conclude that bird communities strongly respond to seasonal fluctuations in resource availability, but responses differ between feeding guilds. While frugivores seem to respond flexibly to seasonal fluctuations, for instance by tracking fruit resources across habitat boundaries, insectivorous birds appear to be more susceptible to the expected increase in seasonal fluctuations in resource availability. 相似文献
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147.
Erik J. Ragsdale Natsumi Kanzaki Waltraud Röseler Matthias Herrmann Ralf J. Sommer 《Zoological Journal of the Linnean Society》2013,168(4):671-698
Developmental plasticity is often correlated with diversity and has been proposed as a facilitator of phenotypic novelty. Yet how a dimorphism arises or how additional morphs are added is not understood, and few systems provide experimental insight into the evolution of polyphenisms. Because plasticity correlates with structural diversity in Pristionchus nematodes, studies in this group can test the role of plasticity in facilitating novelty. Here, we describe three new species, Pristionchus fukushimae sp. nov. , Pristionchus hoplostomus sp. nov. , and the hermaphroditic Pristionchus triformis sp. nov. , which are characterized by a novel polymorphism in their mouthparts. In addition to showing the canonical mouth dimorphism of diplogastrid nematodes, comprising a stenostomatous (‘narrow‐mouthed’) and a eurystomatous (‘wide‐mouthed’) form, the new species exhibit forms with six, 12, or intermediate numbers of cheilostomatal plates. Correlated with this polymorphism is another trait that varies among species: whereas divisions between plates are complete in P. triformis sp. nov. , which is biased towards a novel ‘megastomatous’ form comprising 12 complete plates, the homologous divisions in the other new species are partial and of variable length. In a reconstruction of character evolution, a phylogeny inferred from 26 ribosomal protein genes and a partial small subunit rRNA gene supported the megastomatous form of P. triformis sp. nov. as the derived end of a series of split‐plate forms. Although split‐plate forms were normally only observed in eurystomatous nematodes, a single 12‐plated stenostomatous individual of P. hoplostomus sp. nov. was also observed, suggesting independence of the two types of mouth plasticity. By introducing these new species to the Pristionchus model system, this study provides further insight into the evolution of polymorphisms and their evolutionary intermediates. © 2013 The Linnean Society of London 相似文献
148.
Sebastian Peter Matthias Kinne René Ullrich Gernot Kayser Martin Hofrichter 《Enzyme and microbial technology》2013,52(6-7):370-376
Unspecific peroxygenases (EC 1.11.2.1) represent a group of secreted heme-thiolate proteins that are capable of catalyzing the mono-oxygenation of diverse organic compounds, using only H2O2 as a co-substrate. Here we show that the peroxygenase secreted by the fungus Agrocybe aegerita catalyzed the oxidation of 20 different alkenes. Five branched alkenes, among them 2,3-dimethyl-2-butene and cis-2-butene, as well as propene and butadiene were epoxidized with complete regioselectivity. Longer linear alkenes with a terminal double bond (e.g. 1-octene) and cyclic alkenes (e.g. cyclohexene) were converted into the corresponding epoxides and allylic hydroxylation products; oxidation of the cyclic monoterpene limonene yielded three oxygenation products (two epoxides and an alcohol). In the case of 1-alkenes, the conversion occurred with moderate stereoselectivity, in which the preponderance for the (S)-enantiomer reached up to 72% ee for the epoxide product. The apparent Michaelis–Menten constant (Km) for the epoxidation of the model substrate 2-methyl-2-butene was 5 mM, the turnover number (kcat) 1.3 × 103 s?1 and the calculated catalytic efficiency, kcat/Km, was 2.5 × 105 M?1 s?1. As epoxides represent chemical building blocks of high relevance, new enzymatic epoxidation pathways are of interest to complement existing chemical and biotechnological approaches. Stable and versatile peroxygenases as that of A. aegerita may form a promising biocatalytic platform for the development of such enzyme-based syntheses. 相似文献
149.
150.
Michael E. Böttcher Bo Thamdrup Matthias Gehre Alexandra Theune 《Geomicrobiology journal》2013,30(5):219-226
In the present study, coupled stable sulfur and oxygen isotope fractionation during elemental sulfur disproportionation according to the overall reaction: 4H2O + 4S? → 3H2S + SO4 2 ? + 2H+, was experimentally investigated for the first time using a pure culture of the sulfate reducer Desulfobulbus propionicus at 35?C. Bacterial disproportionation of elemental sulfur is an important process in the sulfur cycle of natural surface sediments and leads to the simultaneous formation of sulfide and sulfate. A dual-isotope approach considering both sulfur and oxygen isotope discrimination has been shown to be most effective in evaluating specific microbial reactions. The influence of iron- and manganese bearing-solids (Fe(II)CO3, Fe(III)OOH, Mn(IV)O2) acting in natural sediments as scavengers for hydrogen sulfide, was considered, too. Disproportionation of elemental sulfur was observed in the presence of iron solids at a cell-specific sulfur disproportionation rate of about 10? 9.5± 0.4 μ mol S? cell? 1 h? 1. No disproportionation, however, was observed with MnO2. In the presence of iron solids, newly formed sulfate was enriched in 18 O compared to water by about +21‰ (≡ ? H2O ), in agreement with a suggested oxygen isotope exchange via traces of intra- or extracellular sulfite that is formed as a disproportionation intermediate. Dissolved sulfate was also enriched in 34S compared to elemental sulfur by up to +35%. Isotope fractionation by Desulfobulbus propionicusis highest for all disproportionating bacteria investigated, so far, and may impact on the development of isotope signals at the redox boundary of surface sediments. 相似文献