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71.
Fluorescence lifetime and intensity quenching studies of human plasma apolipoprotein A-I (apo A-I) in aqueous solution and in recombinant lipoprotein complexes with dimyristoylphosphatidylcholine (DMPC) indicate differences in conformational dynamics. In aqueous solution, the bimolecular quenching constants (k*) for lipid-free apo A-I fluorescence quenching by oxygen and acrylamide are 2.4 X 10(9) and 0.38 X 10(9) M-1 s-1, respectively. These values are independent of the oligomeric form of the protein. There is no correlation between the relatively small k* for apo A-I, which reflects rapid, low-amplitude protein fluctuations, and the labile conformational changes of apo A-I folding reactions, like denaturation, which occur on a slower time scale. In recombinant DMPC/apo A-I complexes (100:1 molar ratio) the protein increases in amphiphilic alpha-helical structure as it blankets the lipid matrix. The apparent k* for oxygen quenching of apo A-I fluorescence in the complex is large and increases in a temperature-dependent manner. We have introduced a two-compartment model, which discriminates the source of quencher molecules as aqueous or lipid, to describe oxygen quenching of DMPC/apo A-I fluorescence. The magnitude and temperature dependence of the apparent k* predominantly reflect the partitioning of oxygen between the two phases rather than being a probe of the lipid physical state. Calculations of the helical hydrophobic moment in apo A-I indicate that tryptophan residues 8 and 72 occur at the lipid-protein interface of amphiphilic alpha-helices, whereas the other two tryptophan residues (50, 108) lie on the nonpolar faces of amphiphilic helices.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
72.
73.
Dye-binding assays that are used to evaluate anti-aggregation ability of small molecule inhibitors towards amyloids are known to be prone to false-positive effects due to spectral overlaps between the dye and the inhibitor. Aza-BODIPY dye, which has both excitation and emission maxima above 600 nm, exhibits a significant increase in its fluorescence intensity in the presence of soluble oligomers of Aβ1–42. These results indicate that aza-BODIPY could serve as a near-IR probe for detecting conformational changes of Aβ1–42 soluble oligomers in vitro, and it should eliminate false-positive effects that are associated with currently utilized thioflavin T-based dyes. In addition, a facile synthesis of aza-BODIPY has been developed, which might further expand the applications of this dye. 相似文献
74.
75.
Nigel E. Gapper Simon A. Coupe Marian J. McKenzie Ben K. Sinclair Ross E. Lill Paula E. Jameson 《Journal of Plant Growth Regulation》2005,24(3):153-165
Broccoli (Brassica oleracea var. italica) deteriorates rapidly following harvest. The two plant hormones ethylene and cytokinin are known to act antagonistically
on harvest-induced senescence in broccoli: ethylene by accelerating the process, and cytokinin by delaying it. To determine
the level at which these hormones influenced senescence, we isolated and monitored the expression of genes normally associated
with senescence in broccoli florets treated with exogenous 6-benzyl aminopurine (6-BAP), 1-aminocyclopropane-1-carboxylic
acid (ACC), a combination of 6-BAP and ACC, and sucrose, in the five days following harvest. Exogenous 6-BAP caused both a
reduction (BoACO) and an increase (BoACS) in ethylene biosynthetic gene expression. The expression of genes used as senescence markers, BoCP5 and BoMT1, was reduced, whereas BoCAB1 levels were maintained after harvest in response to exogenous 6-BAP. In addition, the expression of genes encoding sucrose
transporters (BoSUC1 and BoSUC2) and carbohydrate metabolizing enzymes (BoINV1 and BoHK1) was also reduced upon 6-BAP feeding. Interestingly, the addition of ACC prevented the 6-BAP-induced increase in expression
of BoACS, but 6-BAP negated the ACC-induced increase in expression of BoACO. The culmination of these results indicates a significant role for cytokinin in the delay of senescence. The implication
that cytokinin regulates postharvest senescence in broccoli by inhibiting ethylene perception and/or biosynthesis, thus regulating
carbohydrate transport and metabolism, as well as senescence-associated gene expression, is discussed and a model presented. 相似文献
76.
Dobson RC Griffin MD Devenish SR Pearce FG Hutton CA Gerrard JA Jameson GB Perugini MA 《Protein science : a publication of the Protein Society》2008,17(12):2080-2090
In recent years, dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52) has received considerable attention from a mechanistic and structural viewpoint. DHDPS catalyzes the reaction of (S)-aspartate-beta-semialdehyde with pyruvate, which is bound via a Schiff base to a conserved active-site lysine (Lys161 in the enzyme from Escherichia coli). To probe the mechanism of DHDPS, we have studied the inhibition of E. coli DHDPS by the substrate analog, beta-hydroxypyruvate. The K (i) was determined to be 0.21 (+/-0.02) mM, similar to that of the allosteric inhibitor, (S)-lysine, and beta-hydroxypyruvate was observed to cause time-dependent inhibition. The inhibitory reaction with beta-hydroxypyruvate could be qualitatively followed by mass spectrometry, which showed initial noncovalent adduct formation, followed by the slow formation of the covalent adduct. It is unclear whether beta-hydroxypyruvate plays a role in regulating the biosynthesis of meso-diaminopimelate and (S)-lysine in E. coli, although we note that it is present in vivo. The crystal structure of DHDPS complexed with beta-hydroxypyruvate was solved. The active site clearly showed the presence of the inhibitor covalently bound to the Lys161. Interestingly, the hydroxyl group of beta-hydroxypyruvate was hydrogen-bonded to the main-chain carbonyl of Ile203. This provides insight into the possible catalytic role played by this peptide unit, which has a highly strained torsion angle (omega approximately 201 degrees ). A survey of the known DHDPS structures from other organisms shows this distortion to be a highly conserved feature of the DHDPS active site, and we propose that this peptide unit plays a critical role in catalysis. 相似文献
77.
Wright CM Chovatiya RJ Jameson NE Turner DM Zhu G Werner S Huryn DM Pipas JM Day BW Wipf P Brodsky JL 《Bioorganic & medicinal chemistry》2008,16(6):3291-3301
The Hsp70 molecular chaperones are ATPases that play critical roles in the pathogenesis of many human diseases, including breast cancer. Hsp70 ATP hydrolysis is relatively weak but is stimulated by J domain-containing proteins. We identified pyrimidinone-peptoid hybrid molecules that inhibit cell proliferation with greater potency than previously described Hsp70 modulators. In many cases, anti-proliferative activity correlated with inhibition of J domain stimulation of Hsp70. 相似文献
78.
Georgianna L. Martin Justin A. Ross Shelley D. Minteer David M. Jameson Michael J. Cooney 《Carbohydrate polymers》2009,77(4):695-702
In this work we use the steady state and time-resolved fluorescence of free and enzyme-bound fluorophores to characterize the binding capacity of both unmodified and hydrophobically modified chitosan polymers. Additionally, fluorescence emission is used to qualitatively characterize the extent to which hydrophobic modification of the chitosan polymer affects the relative polarity of the resultant amphiphillic micelles. In total, these results are used to describe how fluorescence techniques can be used to characterize the chemical microenvironment provided by immobilization polymers such as chitosan. Commentary is also given on how this information can be correlated to enzyme activity and spatial distribution during the immobilization processes. 相似文献
79.
80.
Mark Stanback Austin Mercandante Wesley Anderson Howell Burke Rebecca Jameson 《Journal of avian biology》2009,40(6):650-652
Nest boxes provide sheltered nesting sites for both passerines and paper wasps. Although neither wasps nor birds appear to evict the other once one is fully established, it is unclear which is the dominant competitor at the onset of the breeding season. Using wire mesh, we excluded birds but not golden paper wasps Polistesfuscatus from alternating boxes along a transect through edge habitat in North Carolina from 2006 – 2008. If wasps dominate Carolina chickadees Poecile carolinensis and eastern bluebirds Sialia sialis during the early spring (all have similar nest initiation dates), we would expect wasps to settle in both box types at equal frequencies. However, if birds dominate wasps, we would expect wasp nests to be concentrated in “bird‐proof” boxes. We found wasps in bird‐proof boxes significantly more often than in bird‐accessible boxes, indicating that secondary‐cavity nesting birds are able to exclude wasps from available nest sites. Additionally, we found that during the period of nest initiation, birds usurp wasps more often than vice versa. 相似文献