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991.
Increasing free-energy conservation from the conversion of substrate into product is crucial for further development of many biotechnological processes. In theory, replacing the hydrolysis of disaccharides by a phosphorolytic cleavage reaction provides an opportunity to increase the ATP yield on the disaccharide. To test this concept, we first deleted the native maltose metabolism genes in Saccharomyces cerevisiae. The knockout strain showed no maltose-transport activity and a very low residual maltase activity (0.03 μmol mg protein−1 min−1). Expression of a maltose phosphorylase gene from Lactobacillus sanfranciscensis and the MAL11 maltose-transporter gene resulted in relatively slow growth (μaerobic 0.09±0.03 h−1). Co-expression of Lactococcus lactis β-phosphoglucomutase accelerated maltose utilization via this route (μaerobic 0.21±0.01 h−1, μanaerobic 0.10±0.00 h−1). Replacing maltose hydrolysis with phosphorolysis increased the anaerobic biomass yield on maltose in anaerobic maltose-limited chemostat cultures by 26%, thus demonstrating the potential of phosphorolysis to improve the free-energy conservation of disaccharide metabolism in industrial microorganisms. 相似文献
992.
Maity K Venkata BS Kapoor N Surolia N Surolia A Suguna K 《Journal of structural biology》2011,176(2):238-249
The β-hydroxyacyl-acyl carrier protein dehydratase of Plasmodium falciparum (PfFabZ) catalyzes the third and important reaction of the fatty acid elongation cycle. The crystal structure of PfFabZ is available in hexameric (active) and dimeric (inactive) forms. However, PfFabZ has not been crystallized with any bound inhibitors until now. We have designed a new condition to crystallize PfFabZ with its inhibitors bound in the active site, and determined the crystal structures of four of these complexes. This is the first report on any FabZ enzyme with active site inhibitors that interact directly with the catalytic residues. Inhibitor binding not only stabilized the substrate binding loop but also revealed that the substrate binding tunnel has an overall shape of “U”. In the crystal structures, residue Phe169 located in the middle of the tunnel was found to be in two different conformations, open and closed. Thus, Phe169, merely by changing its side chain conformation, appears to be controlling the length of the tunnel to make it suitable for accommodating longer substrates. The volume of the substrate binding tunnel is determined by the sequence as well as by the conformation of the substrate binding loop region and varies between organisms for accommodating fatty acids of different chain lengths. This report on the crystal structures of the complexes of PfFabZ provides the structural basis of the inhibitory mechanism of the enzyme that could be used to improve the potency of inhibitors against an important component of fatty acid synthesis common to many infectious organisms. 相似文献
993.
Bonhomme J Le Goff L Lemée V Gargala G Ballet JJ Favennec L 《Parasitology international》2011,60(3):327-330
The intestinal protozoan Giardia duodenalis includes 2 genetically distinct assemblages, A and B, which are responsible for human infections. Little is known so far on the genotypes of G. duodenalis human isolates in France. The present characterization of 19 French clinical isolates was aimed at determining their genotype patterns and associations with clinical symptoms, and in vivo metronidazole resistance, respectively. Based on both triose-phosphate isomerase (tpi) and β-giardin (bg) gene sequences, twelve isolates were identified as assemblage A, and 7 as assemblage B for the 2 gene loci. Sub-genotyping heterogeneities were observed in 15/19 isolates attributed to either A or B assemblage. They include frequent mismatches and intra-assemblage discordances and mixed positions, which were found more frequently in tpi than in bg sequences, and in assemblage B than in assemblage A sequences. No association was found between sub-genotypes, clinical symptoms and metronidazole sensitivity. Present data underline the need for improvements in the standardization of G. duodenalis multilocus genotyping approach for further molecular epidemiologic studies of giardiasis. 相似文献
994.
995.
Quantitative proteomics of the integrin adhesome show a myosin II-dependent recruitment of LIM domain proteins 总被引:1,自引:0,他引:1
A characteristic of integrins is their ability to transfer chemical and mechanical signals across the plasma membrane. Force generated by myosin II makes cells able to sense substrate stiffness and induce maturation of nascent adhesions into focal adhesions. In this paper, we present a comprehensive proteomic analysis of nascent and mature adhesions. The purification of integrin adhesion complexes combined with quantitative mass spectrometry enabled the identification and quantification of known and new adhesion-associated proteins. Furthermore, blocking adhesion maturation with the myosin II inhibitor blebbistatin markedly impaired the recruitment of LIM domain proteins to integrin adhesion sites. This suggests a common recruitment mechanism for a whole class of adhesion-associated proteins, involving myosin II and the zinc-finger-type LIM domain. 相似文献
996.
Grozav AG Willard BB Kozuki T Chikamori K Micluta MA Petrescu AJ Kinter M Ganapathi R Ganapathi MK 《Proteomics》2011,11(5):829-842
Topoisomerase (topo) II catalyzes topological changes in DNA. Although both human isozymes, topo IIα and β are phosphorylated, site‐specific phosphorylation of topo IIβ is poorly characterized. Using LC‐MS/MS analysis of topo IIβ, cleaved with trypsin, Arg C or cyanogen bromide (CNBr) plus trypsin, we detected four +80‐Da modified sites: tyr656, ser1395, thr1426 and ser1545. Phosphorylation at ser1395, thr1426 and ser1545 was established based on neutral loss of H3PO4 (?98 Da) in the CID spectra and on differences in 2‐D‐phosphopeptide maps of 32P‐labeled wild‐type (WT) and S1395A or T1426A/S1545A mutant topo IIβ. However, phosphorylation at tyr656 could not be verified by 2‐D‐phosphopeptide mapping of 32P‐labeled WT and Y656F mutant protein or by Western blotting with phosphotyrosine‐specific antibodies. Since the +80‐Da modification on tyr656 was observed exclusively during cleavage with CNBr and trypsin, this modification likely represented bromination, which occurred during CNBr cleavage. Re‐evaluation of the CID spectra identified +78/+80‐Da fragment ions in CID spectra of two peptides containing tyr656 and tyr711, confirming bromination. Interestingly, mutation of only tyr656, but not ser1395, thr1326 or ser1545, decreased topo IIβ activity, suggesting a functional role for tyr656. These results, while identifying an important tyrosine in topo IIβ, underscore the importance of careful interpretation of modifications having the same nominal mass. 相似文献
997.
李银平秦俭王晶江利王涛 《现代生物医学进展》2011,11(12):2273-2275
目的:研究乳酸和急性生理学及慢性健康状况评分(APACHE Ⅱ评分)对老年脓毒症患者预后的评估作用。方法:老年脓毒症患者96例,按照入院时血乳酸值分成升高者60例,乳酸正常者36例,比较两组的病死率、休克、机械通气和MODS发生率、APACHE Ⅱ评分的区别;根据APACHE Ⅱ评分(<15、15~24、≥25)分为3组,比较每组患者的病情和预后区别。结果:乳酸升高组老年脓毒症患者的机械通气、休克发生率、MODS发生率、APACHE Ⅱ评分明显大于乳酸正常组(P<0.05),病死率明显上升(28.3%vs 2.7%),(P=0.005);随着APACHE Ⅱ评分增高,患者病情逐渐加重,休克发生率和住院病死率明显升高,(P<0.05),患者乳酸水平也明显增高(P<0.05)。结论:血乳酸和APACHE Ⅱ评分都可以评估老年脓毒症患者病情严重和预后,两者升高提示预后差。 相似文献
998.
目的:观察比较持续皮下输注赖脯胰岛素与常规注射预混赖脯胰岛素对老年非初诊2型糖尿病患者的疗效与安全性。方法:将58例老年2型糖尿病患者随机分为观察组(29例)与对照组(29例),观察组用赖脯胰岛素经胰岛素泵持续皮下输注(CSI-I),对照组用精蛋白锌重组赖脯胰岛素25注射液,2次/d,常规皮下注射。两组患者均给予糖尿病教育、饮食控制及适量运动,共治疗2周。比较治疗前后两组患者的血糖、胰岛素用量、血糖达标时间以及低血糖发生率。结果:治疗后两组患者空腹血糖、餐后血糖均较治疗前下降(P<0.05),观察组血糖达标时间、胰岛素用量均明显低于对照组(P<0.05)。两组低血糖发生率无明显差异。结论:持续皮下输注赖脯胰岛素具有较好的疗效与安全性,是控制老年非初诊2型糖尿病患者较佳的方法。 相似文献
999.
The constructs of atypical depression, bipolar II disorder and borderline
personality disorder (BPD) overlap. We explored the relationships between
these constructs and their temperamental underpinnings. We examined 107 consecutive
patients who met DSM-IV criteria for major depressive episode with atypical
features. Those who also met the DSM-IV criteria for BPD (BPD+), compared
with those who did not (BPD-), had a significantly higher lifetime comorbidity
for body dysmorphic disorder, bulimia nervosa, narcissistic, dependent and
avoidant personality disorders, and cyclothymia. BPD+ also scored higher on
the Atypical Depression Diagnostic Scale items of mood reactivity, interpersonal
sensitivity, functional impairment, avoidance of relationships, other rejection
avoidance, and on the Hopkins Symptoms Check List obsessive-compulsive, interpersonal
sensitivity, anxiety, anger-hostility, paranoid ideation and psychoticism
factors. Logistic regression revealed that cyclothymic temperament accounted
for much of the relationship between atypical depression and BPD, predicting
6 of 9 of the defining DSM-IV attributes of the latter. Trait mood lability
(among BPD patients) and interpersonal sensitivity (among atypical depressive
patients) appear to be related as part of an underlying cyclothymic temperamental
matrix. 相似文献
1000.
Silicon in Equisetum arvense sap has low molar mass and is probably monomeric silicic acid. Tris(β-thujaplicine)silicon X complexes (X Cl, I3) were synthesized but could not be found in extracts of Thuja plicata. 相似文献