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91.
The contribution of each residue of the potato carboxypeptidase inhibitor (PCI) secondary binding site to the overall properties of this protein has been examined using alanine-scanning mutagenesis. Structural and enzymatic studies, performed on a series of PCI mutants, demonstrate that the proper positioning of the primary site for efficient binding and inhibition of carboxypeptidase A is significantly dependent on such a secondary contact region. The aromatic residues in this region play a key role in the stabilization of the PCI-enzyme complex, whereas polar residues contribute little to this task. A comparative study of the oxidative folding of these PCI mutants has been carried out using the disulfide quenching approach. The data, together with the structural characterization of some of these mutants, clearly indicate that noncovalent forces drive the refolding of this small disulfide-rich protein at the reshuffling stage, the rate-limiting step of the process. Moreover, it reveals that by introducing new noncovalent intramolecular contacts in PCI, we may create more stable variants, which also show improved folding efficiency. Taken together, the collected results clarify the folding determinants of the primary and secondary binding sites of PCI and their contribution to the inhibition of the carboxypeptidase, providing clues about PCI evolution and knowledge for its biotechnological redesign. 相似文献
92.
Arolas JL Bronsoms S Lorenzo J Aviles FX Chang JY Ventura S 《The Journal of biological chemistry》2004,279(36):37261-37270
The oxidative folding and reductive unfolding pathways of leech carboxypeptidase inhibitor (LCI; four disulfides) have been characterized in this work by structural and kinetic analysis of the acid-trapped folding intermediates. The oxidative folding of reduced and denatured LCI proceeds rapidly through a sequential flow of 1-, 2-, 3-, and 4-disulfide (scrambled) species to reach the native form. Folding intermediates of LCI comprise two predominant 3-disulfide species (designated as III-A and III-B) and a heterogeneous population of scrambled isomers that consecutively accumulate along the folding reaction. Our study reveals that forms III-A and III-B exclusively contain native disulfide bonds and correspond to stable and partially structured species that interconvert, reaching an equilibrium prior to the formation of the scrambled isomers. Given that these intermediates act as kinetic traps during the oxidative folding, their accumulation is prevented when they are destabilized, thus leading to a significant acceleration of the folding kinetics. III-A and III-B forms appear to have both native disulfides bonds and free thiols similarly protected from the solvent; major structural rearrangements through the formation of scrambled isomers are required to render native LCI. The reductive unfolding pathway of LCI undergoes an apparent all-or-none mechanism, although low amounts of intermediates III-A and III-B can be detected, suggesting differences in protection against reduction among the disulfide bonds. The characterization of III-A and III-B forms shows that the former intermediate structurally and functionally resembles native LCI, whereas the III-B form bears more resemblance to scrambled isomers. 相似文献
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Aurora Arrúe Ricardo Dávila Mercedes Zumárraga Nieves Basterreche Miguel A. González-Torres Biotza Goienetxea Maria I. Zamalloa Juan B. Anguiano José Guimón 《Neurochemical research》2010,35(2):247-253
We have determined the plasma (p) concentration of gamma-aminobutyric acid (GABA) and the dopamine metabolite homovanillic
acid (HVA), and the pHVA/pGABA ratio in schizophrenic and bipolar patients. The research was undertaken in a geographic area
with an ethnically homogeneous population. The HVA plasma concentrations were significantly elevated in the schizophrenic
patients compared to the bipolar patients. The levels of pGABA was significantly lower in the two groups of patients compared
to the control group, while the pHVA/pGABA ratio was significantly greater in the both groups of patients compared to the
controls. As the levels of pHVA and pGABA are partially under genetic control it is better to compare their concentrations
within an homogeneous population. The values of the ratio pHVA/pGABA are compatible with the idea of an abnormal dopamine-GABA
interaction in schizophrenic and bipolar patients. The pHVA/pGABA ratio may be a good peripheral marker in psychiatric research. 相似文献
95.
Strahil Berkov Atanas Pavlov Vasil Georgiev Jost Weber Thomas Bley Francesc Viladomat Jaume Bastida Carles Codina 《Plant Physiology and Biochemistry》2010,48(10-11):827-835
Calli, shoot-clumps and regenerated plants were initiated from young fruits of Pancratium maritimum L. Their genetic stability was monitored by flow cytometry before chemical studies. Apolar metabolites (alkaloids extracted at pH > 7, free fatty acids and fatty alcohols, sterols etc.) were qualitatively and quantitatively analyzed by GC–MS. The results clearly demonstrated that alkaloid synthesis in P. maritimum is closely related with tissue differentiation. The highest amounts of alkaloids and presence of homolycorine and tazettine type compounds (end products of the biosynthetic pathway of the Amaryllidaceae alkaloids) were found in highly differentiated tissues. Galanthamine accumulated in the leaves of plantlets. The amount of hordenine, a protoalkaloid, is related with the ability of tissues to synthesize alkaloids. Saturated fatty acids were found in considerably higher levels in undifferentiated callus cultures and partially differentiated shoot-clumps than in regenerated plants. Mono- and dienoic fatty acids were found at higher levels in non-photosynthesizing tissues – calli, and in vitro and intact bulbs, while α-linolenic acid (trienoic acid) was found in higher amounts in the photosynthesizing leaves of shoot-clumps and regenerated plants than in bulbs and calli. Fatty alcohols were found mainly in leaves, while sterols tended to accumulate in photosynthesizing and undifferentiated tissues. 相似文献
96.
M. Helena Garcia Andreia Valente Tânia S. Morais M. Teresa Duarte Francesc X. Avilés 《Inorganica chimica acta》2010,363(14):3765-3775
A new family of Ru(II) mixed metallocene complexes of the type [Ru(η5-C5H5)(η6-arene)][PF6] has been synthesized and fully characterized by NMR and UV-Vis spectroscopy. X-ray analysis of single crystal was achieved for all the complexes and revealed the presence of two enantiomers expected for planar chirality originated by the η6 coordination of the arene prochiral ligands. Studies of interaction of the new complexes with pBR322 DNA by atomic force microscopy showed very strong and different types of interaction. Antiproliferative tests were examined on human leukemia cancer cells (HL-60) using the MTT assay, and the IC50 values revealed low antiproliferative activity compared to cisplatin. 相似文献
97.
Turró S Ingelmo-Torres M Estanyol JM Tebar F Fernández MA Albor CV Gaus K Grewal T Enrich C Pol A 《Traffic (Copenhagen, Denmark)》2006,7(9):1254-1269
Alcoholic and nonalcoholic liver steatosis and steatohepatitis are characterized by the massive accumulation of lipid droplets (LDs) in the cytosol of hepatocytes. Although LDs are ubiquitous and dynamic organelles found in the cells of a wide range of organisms, little is known about the mechanisms and sites of LD biogenesis. To examine the participation of these organelles in the pathophysiological disorders of steatotic livers, we used a combination of mass spectrometry (matrix-assisted laser desorption ionization-time of flight and LC-MS electrospray) and Western blot analysis to study the composition of LDs purified from rat liver after a partial hepatectomy. Fifty proteins were identified. Adipose differentiation-related protein was the most abundant, but other proteins such as calreticulin, TIP47, Sar1, Rab GTPases, Rho and actin were also found. In addition, we identified protein associated with lipid droplets I ALDI (tentatively named Associated with LD protein 1), a novel protein widely expressed in liver and kidney corresponding to the product of 0610006F02Rik (GI:27229118). Our results show that, upon lipid loading of the cells, ALDI translocates from the endoplasmic reticulum into nascent LDs and indicate that ALDI may be targeted to the initial lipid deposits that eventually form these droplets. Moreover, we used ALDI expression studies to view other processes related to these droplets, such as LD biogenesis, and to analyze LD dynamics. In conclusion, here we report the composition of hepatic LDs and describe a novel bona fide LD-associated protein that may provide new insights into the mechanisms and sites of LD biogenesis. 相似文献
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