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81.
Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities. 总被引:1,自引:0,他引:1
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A. J. Scheidig T. R. Hynes L. A. Pelletier J. A. Wells A. A. Kossiakoff 《Protein science : a publication of the Protein Society》1997,6(9):1806-1824
The crystal structures of the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) complexed to bovine chymotrypsin (C-APPI) and trypsin (T-APPI) and basic pancreatic trypsin inhibitor (BPTI) bound to chymotrypsin (C-BPTI) have been solved and analyzed at 2.1 A, 1.8 A, and 2.6 A resolution, respectively. APPI and BPTI belong to the Kunitz family of inhibitors, which is characterized by a distinctive tertiary fold with three conserved disulfide bonds. At the specificity-determining site of these inhibitors (P1), residue 15(I)4 is an arginine in APPI and a lysine in BPTI, residue types that are counter to the chymotryptic hydrophobic specificity. In the chymotrypsin complexes, the Arg and Lys P1 side chains of the inhibitors adopt conformations that bend away from the bottom of the binding pocket to interact productively with elements of the binding pocket other than those observed for specificity-matched P1 side chains. The stereochemistry of the nucleophilic hydroxyl of Ser 195 in chymotrypsin relative to the scissile P1 bond of the inhibitors is identical to that observed for these groups in the trypsin-APPI complex, where Arg 15(I) is an optimal side chain for tryptic specificity. To further evaluate the diversity of sequences that can be accommodated by one of these inhibitors, APPI, we used phage display to randomly mutate residues 11, 13, 15, 17, and 19, which are major binding determinants. Inhibitors variants were selected that bound to either trypsin or chymotrypsin. As expected, trypsin specificity was principally directed by having a basic side chain at P1 (position 15); however, the P1 residues that were selected for chymotrypsin binding were His and Asn, rather than the expected large hydrophobic types. This can be rationalized by modeling these hydrophilic side chains to have similar H-bonding interactions to those observed in the structures of the described complexes. The specificity, or lack thereof, for the other individual subsites is discussed in the context of the "allowed" residues determined from a phage display mutagenesis selection experiment. 相似文献
82.
Roman Bo?a Peter Baran L'ubor Dlháň Hartmut Fuess Wolfgang Haase Franz Renz Wolfgang Linert Ingrid Svoboda Rüdiger Werner 《Inorganica chimica acta》1997,260(2):4119-136
The structure of the [Fe(bzimpy)2](ClO4)2·xH2O system (x = 0.25) was determined by single crystal X-ray structure analysis. The Fe(II) ion is hexacoordinated by six donor nitrogen atoms. The magnetic properties of the complex were investigated by powder magnetic susceptibility measurements and ESR. The freshly prepared sample does not show any traces of iron(III) impurities but these are formed as a function of time. After 1 year the sample contains 8.2% iron(III) as shown by UV spectroscopy and indicated by geff = 4.3 and 2.0 in its ESR spectrum. This explains the recorded ξ versus T behaviour at low temperature: with increasing temperature the ξ value decreases according to the Curie-Weiss law for a S = 5/2 system having an effective g = 4.3. Above 220 K a continuous increase in the ξ value is observed and a spin crossover applies. The spin transition is not complete at room temperature. A pronounced hysteresis is observed upon heating/cooling the sample between 220 and 414 K on the basis of magnetic data and infrared spectra. 相似文献
83.
Maurizio Zandomeneghi 《Chirality》1995,7(6):446-451
Complexation of 2-(3′-benzoylphenyl)propionic acid (ketoprofen), 1 , to bovine serum albumin (BSA) results in an intense negative circular dichroism in the ketonic n → π* band of the benzoylphenyl moiety. This high CD contrasts with the weak CD of 1 -enantiomers dissolved in common solvents. Furthermore, a number of chiral and achiral molecules containing the benzophenone moiety are easily complexed to BSA: all these complexes show an intense CD at the same transition. To account for the observed CD intensities of the above molecules, it appears that BSA complexation markedly shifts the equilibrium between strongly asymmetric, antipodic conformers. Dissymmetry of these conformers is connected to the instability of a structure with phenyl rings coplanar to the carbonyl chromophore, as also indicated by molecular mechanics calculations. The magnification of the Cotton effects of the 1 -antipodes, due to the protein, can be used to measure the optical purity of 1 -samples with excellent precision. In contrast with BSA, human SA is unable to recognize the chirality of 1 -antipodes; oleic acid cocomplexation modifies this fact as well as other features of the binding. © 1995 Wiley-Liss, Inc. 相似文献
84.
Solubilities and transfer chemical potentials of carboplatin, cisplatin, iproplatin, and several related platinum complexes have been determined in methanol-water mixtures. the range of solvation behaviour is discussed in relation to possible oral administration of complexes of this type. 相似文献
85.
Bo Lönnerdal Barbara O. Schneeman Carl L. Keen Lucille S. Hurley 《Biological trace element research》1980,2(3):149-158
Rat bile and pancreatic fluid were examined for the presence of low molecular weight zinc complexes. Fluids were collected
separately by cannulation, and zinc distribution in collected samples was analyzed by gel filtration on Sephadex G-50. Most
of the zinc in bile was associated with low molecular weight zinc complexes; only a small amount of zinc was present in the
high molecular weight fraction. In contrast, pancreatic secretions did not contain low molecular weight zinc complexes, but
there were considerable amounts of zinc bound to high molecular weight compounds. The addition of zinc to bile resulted in
an increased amount of zinc in the low molecular weight fraction, while the addition of zinc to pancreatic fluid resulted
primarily in an increase in zinc bound to the high molecular weight components. Like pancreatic fluid, homogenates of pancreatic
tissue had no low molecular weight zinc complex. In rats whose bile and pancreatic fluid were removed and not returned into
the intestine, the amount of zinc bound to low molecular weight complexes in intestinal homogenates was reduced. This alteration
of the molecular distribution of zinc in intestinal homogenates by removal of bile and pancreatic fluid suggests the potential
importance of low molecular weight zinc complexes for zinc homeostasis. 相似文献
86.
The dissociation products of isolated phycobilisomes of Mastigocladus laminosus were separated and analyzed by ultracentrifugation and, in part, by isoelectric focusing. With the exception of the allophycocyanin core, the sedimentation constants of peripheral phycocyanin- and phycoerythrocyanin-phycocyanin complexes lay in the range of 6 to 17S. The latter was represented by a 17S aggregate of two hexameric phycocyanins (dodecamer, dipartite unit). A complex with an absorption maximum at 610 nm (phycocyanin) and a shoulder at 580 nm (phycoerythrocyanin), a fluorescence emission maximum at 645 nm and a sedimentation constant of 11 S is described as a heterogeneously composed hexamer of ()3-phycoerythrocyanin-()3-phycocyanin. It was stable under extended dissociation in the cold and under isoelectric focusing. An aggregate of 14 S with an absorption maximum at 576 nm and a shoulder in the fluorescence emission spectrum at 625 nm (phycoerythrocyanin) in addition to the maximum at 645 nm (phycocyanin) is interpreted as a polar phycoerythrocyanin/ phycoerythrocyanin-phycocyanin complex. Combining these complexes with phycocyanin dodecamers creates peripheral rods of the phycobilisome. A proposal of the phycobiliprotein distribution within the phycobilisome of M. laminosus is presented.Abbreviations APC
allophycocyanin
- PC
phycocyanin
- PE
phycoerythrin
- PEC
phycoerythrocyanin 相似文献
87.
B. H. Li M. Kwasniewski J. Kirchner R. Bockrath 《Molecular & general genetics : MGG》1992,231(3):480-484
Summary Expression of the lacZ gene in Escherichia coli is inactivated by exposure to ultraviolet light (UV). Inactivation is exceptionally effective when cells contain amplified levels of DNA photolyase (which forms complexes with pyrimidine dimers in the absence of light for actual photoreversal) and a prophage. Without amplified photolyase, the prophage or both, inactivation rates are similar and much lower. UV-inactivation of lacZ gene expression in the presence of both amplified photolyase and is even more effective if cI857 is used in place of the wildtype prophage but is wholly unexceptional if the prophage carries defects in the genes rexA or rexB. When Rex AB proteins are provided by expression from a plasmid and the cell also contains amplified photolyase, exceptional inactivation rates again obtain; in fact inactivation is most effective under these conditions. The data are considered to reveal a role for Rex AB proteins, which mediate superinfection exclusion, in the exceptional inactivation of gene expression by photolyase bound to pyrimidine dimers in DNA. Photolyase-dimer complexes may mimic the structure of certain complexes that arise during phage development and thus influence Rex A and/or B proteins, thereby shutting down cell metabolism. 相似文献
88.
Summary Immunocytochemical techniques using colloidal gold as the marker have been used to examine the location of the two light harvesting pigment-protein complexes in cryptophyte chloroplasts. A comparison of post-embedding thin section labelling and freeze fracture labelling has been carried out onRhodomonas salina using polyclonal antibodies to a chlorophylla/c
2 light-harvesting complex, phycoerythrin and the -subunit of phycoerythrin. The effect of different fixation procedures on the intensity of labelling and ac curacy of antigen location have been examined and the effectiveness of uranyl acetate and tannic acid in improving both the preservation of thylakoid structure and labelling density of phycoerythrin has been demonstrated. Freeze fracture labelling gives better spatial res olution of the different antigens than post-embedding labelling, as well as better definition of thylakoid membranes. It confirms the location of phycoerythrin in the thylakoid lumen and the location of the chlorophylla/c
2 LHC in both appressed and unappressed thylakoid membranes.Abbreviations PE
phycoerythrin
- chl
chlorophyll
- LHC
light-har-vesting complex 相似文献
89.
Raúl Alva J. Antonio Lugo-R Eduardo Arzt Jorge Cerbón Blanca E. Rivera Mireya Toro Sergio Estrada-O 《Journal of bioenergetics and biomembranes》1992,24(1):125-129
Nigericin is a monocarboxylic polyether molecule described as a mobile K+ ionophore unable to transport Li+ and Cs+ across natural or artificial membranes. This paper shows that the ion carrier molecule forms complexes of equivalent energy demands with Li+, Cs+, Na+, Rb+, and K+. This is in accordance with the similar values of the complex stability constants obtained from nigericin with the five alkali metal cations assayed. On the other hand, nigericinalkali metal cation binding isotherms show faster rates for Li+ and Cs+ than for Na+, K+, and Rb+, in conditions where the carboxylic proton does not dissociate. Furthermore, proton NMR spectra of nigericin-Li+ and nigericin-Cs+ complexes show wide broadenings, suggesting strong cation interaction with the ionophore; in contrast, the complexes with Na+, K+, and Rb+ show only clear-cut chemical shifts. These latter results support the view that nigericin forms highly stable complexes with Li+ and Cs+ and contribute to the explanation for the inability of this ionophore to transport the former cations in conditions where it catalyzes a fast transport of K+>Rb+>Na+.Part of the results of this paper were presented at the 14th International Congress of Biochemistry in Prague, Czechoslovakia. 相似文献
90.
Robert C. Jennings Flavio M. Garlaschi Paolo D. Gerola Rachel Etzion-Katz Giorgio Forti 《BBA》1981,638(1):100-107
Lowering the pH of the incubation medium to pH 5.4 leads to grana formation morphologically similar to that induced by metal cations. The same phenomenon is observed in EDTA-washed chloroplasts, indicating that it is not due in part to electrostatic ‘masking’ by residual cations associated with the membranes. Digitonin fractionation studies have indicated that the distribution of the major chlorophyll-protein complexes between granal and stromal membrane regions is similar at pH 5.4 in the absence of Mg2+, and at pH 7.4 in the presence of Mg2+. Chlorophyll fluorescence induction studies have indicated that the primary photochemistry of Photosystem II (PS II) is stimulated by lowering the pH to 5.4, just as it is upon metal cation addition at higher pH values. The failure to observe such an increase at pH 5.4 by measuring electron transport to ferricyanide is attributed to a combination of an inhibition by this pH of electron transport at a site after Q reduction and an increase in the number of PS II centres detached from the plastoquinone pool. We conclude that the stacked configuration of chloroplast membranes leads to increased PS II primary photochemistry, which is most simply explained in terms of a redistribution of excitation energy towards PS II. 相似文献