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31.
Carbon dioxide (CO2), a vital molecule of the carbon cycle, is a critical component in living organisms’ metabolism, performing functions that lead to the building of compounds fundamental for the life cycle. In all living organisms, the CO2/bicarbonate (HCO3−) balancing is governed by a superfamily of enzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the pivotal physiological reaction, consisting of the reversible hydration of the CO2 to HCO3− and protons. Opportunistic and pathogenic fungi can sense the environmental CO2 levels, which influence their virulence or environmental subsistence traits. The fungal CO2-sensing is directly stimulated by HCO3− produced in a CA-dependent manner, which directly activates adenylyl cyclase (AC) involved in the fungal spore formation. The interference with CA activity may impair fungal growth and virulence, making this approach interesting for designing antifungal drugs with a novel mechanism of action: the inhibition of CAs linked to the CO2/HCO3−/pH chemosensing and signaling. This review reports that sulfonamides and their bioisosteres as well as inorganic anions can inhibit in vitro the β- and α-CAs from the fungi, suggesting how CAs may be considered as a novel “pathogen protein” target of many opportunistic, pathogenic fungi. 相似文献
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33.
为了克服碳素墨汁、磷化剂等传统吸光涂料吸光率低、污染环境的缺点,作者研制了一种激光热处理用新型的吸光涂料,并将该涂料与碳素墨汁进行了比较研究,结果表明,这种飞机色涂料具有手感细腻、与金属基体结合牢固、干燥快、无毒、无刺激性气味、环境友好、易清除等优点,且对10.6μm波长的CO_2激光的吸收率达85%以上,而碳素墨汁的吸光率只有30%,在相同工艺条件下,涂有新型涂料试样激光淬火后的硬化区面积和硬化层深度分别为3.44mm~2和1.05mm,而碳素墨汁分别为1.01mm~2和0.32mm;涂有新型涂料试样激光淬火后表面洛氏硬度平均为HRC57.6,而碳素墨汁平均为HRC38.6;涂有新型涂料的试样无论聚集法还是宽带法激光淬火后,其表层压应力均大于碳素墨汁,且涂有新型涂料的试样表层的最大压应力为-429MPa。 相似文献
34.
Ippolito Joseph A.; Nair Satish K.; Alexander Richard S.; Kiefer Laura L.; Fierke Carol A.; Christianson David W. 《Protein engineering, design & selection : PEDS》1995,8(10):975-980
The structure of histidine 94aspartate (H94D) carbonic anhydraseII (CAII) crystallized in an orthorhombic space group has beendetermined to 2.5 Å resolution. This crystal form is notisomorphous with monoclinic wild-type enzyme crystals or withthe monoclinic crystal form of H94D CAII reported earlier [Kiefer,L.L.,Ippolito,J.A., Fierke,C.A. and Christianson,D.W. (1993) J. Am.Chem. Soc., 115, 1258112582]. In monoclinic H94D CAII,a fully occupied zinc ion is tetrahedrally coordinated by D94,H96, H119 and a water molecule. In orthorhombic H94D CAII, apartially occupied zinc ion is coordinated by H96 and H119 andonly weakly coordinated by a disordered D94 side chain.Thesedifferences are particularly surprising given that the two crystalforms co-precipitate in the same drop in the same experiment.Re-refinement of the orthorhombic crystal form of H94C CAIIand comparison with its corresponding monoclinic crystal formyield similar results. It appears that partialbut notfullzinc dissociation accompanies the crystallizationof CAII variants in the orthorhombic crystal form, and significantdifferences on the protein surface presumably affect the relativestability of each crystal lattice. These results underscoreanunexpected ambiguity in this protein engineering experiment:which crystal structure of H94D CAII should be correlated withfunctional measurements made in solution? 相似文献
35.
Bon Il Koo Jae Woong Choi Seuk Young Song Ye Hun Choi Tae Yong Lee Shin-Hyun Kim Ki Jun Jeong Yoon Sung Nam 《Advanced functional materials》2021,31(25):2102497
Mineral carbonation is the most effective carbon capture technique, but carbon dioxide (CO2) conversion is limited by the slow hydration rate of CO2 (<10−1 s−1). A biological solution exists: carbonic anhydrase (CA) efficiently hydrates CO2 at a turnover rate of ≈106 s−1 under ambient conditions, making it an extremely attractive candidate for industrial post-combustion CO2 capture. However, high cost and poor long-term stability impose a technical barrier to its practical uses. Here, a genetically engineered Corynebacterium glutamicum (C. glutamicum) is introduced as a robust cell display platform for the in situ stabilization and low-cost production of CA. The enzyme is displayed in the mycolic layer with porin B as an anchoring protein with (GGGGS)2 as a spacer. The cell-displayed CA exhibits no significant inactivation of the CO2 hydration activity for at least one month at 37 °C. Its denaturation rate constant at 50 °C (0.07) is an order of magnitude lower than that of free CA (0.52–0.54). This study demonstrates that a structurally robust cell template allows the effective stabilization of CA, suggesting the C. glutamicum-based cell display as a promising technique to achieve highly efficient, sustainable, and low-cost CO2 capture for industrial applications. 相似文献
36.
Monika Barathova Katarina Grossmannova Petra Belvoncikova Veronika Kubasova Veronika Simko Rudolf Skubla Lucia Csaderova Jaromir Pastorek 《International journal of molecular sciences》2020,21(22)
The coexistence of cancer and other concomitant diseases is very frequent and has substantial implications for treatment decisions and outcomes. Beta-blockers, agents that block the beta-adrenergic receptors, have been related also to cancers. In the model of multicellular spheroids formed by colorectal cancer cells we described a crosstalk between beta-blockade by propranolol and tumour microenvironment. Non-selective beta-blocker propranolol decreased ability of tumour cells to adapt to hypoxia by reducing levels of HIF1α and carbonic anhydrase IX in 3D spheroids. We indicated a double action of propranolol in the tumour microenvironment by inhibiting the stability of HIF1α, thus mediating decrease of CA IX expression and, at the same time, by its possible effect on CA IX activity by decreasing the activity of protein kinase A (PKA). Moreover, the inhibition of β-adrenoreceptors by propranolol enhanced apoptosis, decreased number of mitochondria and lowered the amount of proteins involved in oxidative phosphorylation (V-ATP5A, IV-COX2, III-UQCRC2, II-SDHB, I-NDUFB8). Propranolol reduced metastatic potential, viability and proliferation of colorectal cancer cells cultivated in multicellular spheroids. To choose the right treatment strategy, it is extremely important to know how the treatment of concomitant diseases affects the superior microenvironment that is directly related to the efficiency of anti-cancer therapy 相似文献
37.
Lucio Panizza Paola Frisenda Alessandra Stefan Marco Francese Alessandra Madeo Elena Martelli Alejandro Hochkoeppler 《化学与化工:英文版》2014,(2):151-156
A new strategy to prevent the biofouling of water-submerged surfaces is presented here. In particular, the authors showthat carbonic anydrase from Methanosarcina thermophila can be entrapped into polyacrylic paints, preserving enzyme activity. In addition, the authors also show that enzyme-containing paints inhibit the growth of marine microorganims, preventing biofouling. 相似文献
38.
Dr. Caibao Jiang Jinguo Shi Liping Liao Liantao Zhang Jiayong Liu Yang Wang Yaoqiang Lao Prof. Jingxia Zhang 《ChemMedChem》2020,15(8):705-715
In this study, 22 novel compounds were designed and synthesized by acetamide bridge chains, among which 5 a – 5 k were monosubstituted compounds, and 6 a – 6 k were disubstituted. A series of biological evaluations was then carried out to determine the carbonic anhydrase inhibitory activity, neuroprotective effects and cytotoxicity of 5 a – 5 k and 6 a – 6 k . The results showed that some compounds could protect PC12 cells from sodium nitroprusside (SNP)-induced damage. In terms of the neuroprotection and inhibitory activity against carbonic anhydrase II, monosubstituted compounds were better than disubstituted. Compound 5 c exhibited better protective effect in PC12 cells than that of edaravone, and 5 c also showed less cytotoxicity. In addition, compound 5 c was found to be the most effective selective carbonic anhydrase II inhibitor (IC50=16.7 nM, CAI/CAII=54.3), which was similar to the inhibitory effect of acetazolamide. Moreover, the selectivity of compound 5 c was better than that of acetazolamide (IC50=12.0 nM, CAI/CAII=20.8). Molecular docking presented that the binding effect of compound 5 c with carbonic anhydrase II was superior to that of 5 c with carbonic anhydrase I and IX, which was consistent with the inhibitory results. Based on above findings, compound 5 c may be a potential candidate for selective carbonic anhydrase II inhibitor, and it had obviously neuroprotective effect and great advantages in drug safety. 相似文献
39.
王华章 《工程抗震与加固改造》2012,(2):86-91
某底框工程由于错误混凝土配合比影响了结构的可靠度,必须进行加固。空间和时间决定了不适合采用传统加固方法。根据结构的不同情况,分别采用碳纤维加固墙梁、外包钢加固柱,对既有结构进行了局部加固。通过观测建筑沉降和墙梁跨中挠度,分析值和观测值基本吻合。结果表明,加固工程具有良好的受力性能,在设计荷载下是安全的。为今后处理类似设计问题提供依据。加固工程受到业主的好评,并通过验收投入使用。 相似文献
40.
Prof. Erden Banoglu Taner Ercanlı Dr. Tuğçe Gür Maz Dr. Daniela Vullo Dr. Alessandro Bonardi Prof. Paola Gratteri Prof. Claudiu T. Supuran 《ChemMedChem》2022,17(10):e202200056
We describe the synthesis of a series of thiadiazolyl-benzenesulfonamide derivatives carrying an aromatic tail linked by an amide linker ( 12–34 ), as human carbonic anhydrase (hCA) inhibitors. These thiadiazol derivatives were evaluated against four physiologically relevant CA isoforms (hCA I, II, IX, and XII), and demonstrated intriguing inhibitory activity against CA II with Ki values in the range of 2.4–31.6 nM. Besides hCA II, also hCA XII activity was potently inhibited by some of the derivatives (Ki=1.5–88.5 nM), producing dual inhibitors of both isoforms. Notably, compound 17 was the most potent dual CA II (Ki=3.1 nM) and XII (Ki=1.5 nM) inhibitor with a significant selectivity ratio over CA I and IX isoforms. In conclusion, although all compounds exhibited preferential activity towards hCA II, the nature of the substituents at the tail part of the main scaffold influenced the activity and selectivity toward other isoforms. 相似文献