| 3041. |
- Jacobson, Frida, 1975, et al.
(författare)
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High resolution X-ray structures of the oxidised and reduced forms of nitrite reductase from Rhodobacter sphaeroides 2.4.3
- 2005
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Ingår i: Acta Crystallography D. - 0907-4449 .- 1399-0047. ; 61, s. 1190-1198
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Tidskriftsartikel (refereegranskat)abstract
- Nitrite reductase is an enzyme operating in the denitrification pathway which catalyses the conversion of nitrite (NO2(-)) to gaseous nitric oxide (NO). Here, crystal structures of the oxidized and reduced forms of the copper-containing nitrite reductase from Rhodobacter sphaeroides 2.4.3 are presented at 1.74 and 1.85 A resolution, respectively. Whereas the structure of the enzyme is very similar to those of other copper-containing nitrite reductases, folding as a trimer and containing two copper sites per monomer, the structures reported here enable conformational differences between the oxidized and reduced forms of the enzyme to be identified. In the type 1 copper site, a rotational perturbation of the side chain of the copper ligand Met182 occurs upon reduction. At the type 2 copper site, a dual conformation of the catalytic residue His287 is observed in the oxidized structure but is lacking in the reduced structure, such that the interactions of the oxidized type 2 copper ion can be regarded as adopting octahedral geometry. These findings shed light on the structural mechanism of the reduction of a copper-bound nitrite to nitric oxide and water.
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| 3042. |
- Jacobson, Frida, 1975, et al.
(författare)
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pH dependence of copper geometry, reduction potential, and nitrite affinity in nitrite reductase
- 2007
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:9, s. 6347-6355
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Tidskriftsartikel (refereegranskat)abstract
- Many properties of copper-containing nitrite reductase are pH-dependent, such as gene expression, enzyme activity, and substrate affinity. Here we use x-ray diffraction to investigate the structural basis for the pH dependence of activity and nitrite affinity by examining the type 2 copper site and its immediate surroundings in nitrite reductase from Rhodobacter sphaeroides 2.4.3. At active pH the geometry of the substrate-free oxidized type 2 copper site shows a near perfect tetrahedral geometry as defined by the positions of its ligands. At higher pH values the most favorable copper site geometry is altered toward a more distorted tetrahedral geometry whereby the solvent ligand adopts a position opposite to that of the His-131 ligand. This pH-dependent variation in type 2 copper site geometry is discussed in light of recent computational results. When co-crystallized with substrate, nitrite is seen to bind in a bidentate fashion with its two oxygen atoms ligating the type 2 copper, overlapping with the positions occupied by the solvent ligand in the high and low pH structures. Fourier transformation infrared spectroscopy is used to assign the pH dependence of the binding of nitrite to the active site, and EPR spectroscopy is used to characterize the pH dependence of the reduction potential of the type 2 copper site. Taken together, these spectroscopic and structural observations help to explain the pH dependence of nitrite reductase, highlighting the subtle relationship between copper site geometry, nitrite affinity, and enzyme activity.
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| 3043. |
- Jacobson, Therese, et al.
(författare)
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Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast.
- 2012
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Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 125:21, s. 5073-83
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Tidskriftsartikel (refereegranskat)abstract
- Several metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.
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| 3044. |
- Jacobsson, S., et al.
(författare)
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Second order symmetry operators for the massive Dirac equation
- 2023
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Ingår i: Classical and Quantum Gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 40:4
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Tidskriftsartikel (refereegranskat)abstract
- Employing the covariant language of two-spinors, we find what conditions a curved four-dimensional Lorentzian spacetime must satisfy for existence of a second order symmetry operator for the massive Dirac equation. The conditions are formulated as existence of a set of Killing spinors satisfying a set of covariant linear differential equations. Using these Killing spinors, we then state the most general form of such an operator. Partial results for the zeroth and first order are presented and interpreted as well. Computer algebra tools from the Mathematica package suite xAct were used for the calculations.
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| 3045. |
- Jafari, Gholamali, et al.
(författare)
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Genetics of extracellular matrix remodeling during organ growth using the Caenorhabditis elegans pharynx model.
- 2010
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Ingår i: Genetics. - : Oxford University Press (OUP). - 1943-2631. ; 186:3, s. 969-82
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Tidskriftsartikel (refereegranskat)abstract
- The organs of animal embryos are typically covered with an extracellular matrix (ECM) that must be carefully remodeled as these organs enlarge during post-embryonic growth; otherwise, their shape and functions may be compromised. We previously described the twisting of the Caenorhabditis elegans pharynx (here called the Twp phenotype) as a quantitative mutant phenotype that worsens as that organ enlarges during growth. Mutations previously known to cause pharyngeal twist affect membrane proteins with large extracellular domains (DIG-1 and SAX-7), as well as a C. elegans septin (UNC-61). Here we show that two novel alleles of the C. elegans papilin gene, mig-6(et4) and mig-6(sa580), can also cause the Twp phenotype. We also show that overexpression of the ADAMTS protease gene mig-17 can suppress the pharyngeal twist in mig-6 mutants and identify several alleles of other ECM-related genes that can cause or influence the Twp phenotype, including alleles of fibulin (fbl-1), perlecan (unc-52), collagens (cle-1, dpy-7), laminins (lam-1, lam-3), one ADAM protease (sup-17), and one ADAMTS protease (adt-1). The Twp phenotype in C. elegans is easily monitored using light microscopy, is quantitative via measurements of the torsion angle, and reveals that ECM components, metalloproteinases, and ECM attachment molecules are important for this organ to retain its correct shape during post-embryonic growth. The Twp phenotype is therefore a promising experimental system to study ECM remodeling and diseases.
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| 3046. |
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| 3047. |
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| 3048. |
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| 3049. |
- Jagers, Peter, 1941, et al.
(författare)
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Branching processes with deteriorating random environments
- 2002
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Ingår i: Journal of Applied Probability. - 0021-9002 .- 1475-6072. ; 39, s. 395-401
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Tidskriftsartikel (refereegranskat)abstract
- We introduce Galton-Watson style branching processes in random environments which are deteriorating rather than stationary or independent. Some primary results on process growth and extinction probability are shown. Two simple examples are given.
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| 3050. |
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