The crystal and molecular structure of the title complex, Cu（ada）2（py）2（H2O）（ada=adamantanecarboxylic group, py=pyridine）, C 32H 42CuN2O5, were determined by XRD. It belongs to monoclinic system with space gro...The crystal and molecular structure of the title complex, Cu（ada）2（py）2（H2O）（ada=adamantanecarboxylic group, py=pyridine）, C 32H 42CuN2O5, were determined by XRD. It belongs to monoclinic system with space group P21/n and crystal cell parameters:a=1.619 9（3）, b=0.680 5（1）, c=2.802 8（6） nm, β=94.15（3）°; V=3.082（1） nm 3, Z=4, Dc=1.289 g/cm3, Mr=589.22, μ（MoKα）=0.750 mm -1, F（000）=1 268. The structure was refined to R=0.057 8 and wR=0.158 1 for 4 447 observed reflections with I≥2σ（I）. The aquo complex is mononuclear with distorted square-pyramidal coordination.展开更多
Adenosine,a critical molecule regulating cellular function both inside and outside cells,is controlled by two human adenosine deaminases:ADA1 and ADA2.While ADA1 primarily resides in the cytoplasm,ADA2 can be transpor...Adenosine,a critical molecule regulating cellular function both inside and outside cells,is controlled by two human adenosine deaminases:ADA1 and ADA2.While ADA1 primarily resides in the cytoplasm,ADA2 can be transported to lysosomes within cells or secreted outside the cell.Patients with ADA2 deficiency(DADA2)often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood.Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages.Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages,and its intracellular concentration decreases in cells secreting TNF-α.This suggests that ADA2 may function as a lysosomal adenosine deaminase,regulating TNF-α expression by the cells.Interestingly,pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage(BAL),correlating with elevated pro-inflammatory cytokine levels.Conversely,cord blood has low ADA2 levels,creating a more immunosuppressive environment.Additionally,secreted ADA2 can bind to apoptotic cells,activating immune cells by reducing extracellular adenosine levels.These findings imply that ADA2 release from monocytes during inflammation,triggered by growth factors,may be crucial for cell activation.Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.展开更多
目的分析中国人群腺苷脱氨酶2缺乏症(deficiency of adenosine deaminase 2,DADA2)致病基因频率,为有效开展中国人群DADA2的防控和干预工作提供依据。方法回顾性分析2015年1月至2021年1月于北京智因东方转化医学研究中心有限公司进行全...目的分析中国人群腺苷脱氨酶2缺乏症(deficiency of adenosine deaminase 2,DADA2)致病基因频率,为有效开展中国人群DADA2的防控和干预工作提供依据。方法回顾性分析2015年1月至2021年1月于北京智因东方转化医学研究中心有限公司进行全外显子组测序的11.1万例原始数据,对ADA2基因致病和可能致病性突变进行携带者筛查,分析ADA2基因杂合突变的类型和等位基因频率。结果发现29种ADA2基因致病和可能致病性杂合突变,其中6种[c.730G>T(p.E244X)、c.1049_c.1061 delAGCTGCCTTACTT(p.K350Tfs*14)、c.940A>T(p.K314X)、c.1239+2(IVS8)T>C、c.1240-1(IVS8)G>A、c.1087C>T(p.Q363X)]既往未见报道,等位基因累计频率为0.58%。人群基因频率最高的为p.F355L(0.5%),其次为p.Y453C(0.014%)和p.P193L(0.013%),其他26种位点均小于0.01%,为罕见突变位点。结论通过筛查丰富了ADA2基因突变谱,明确了中国地区人群的ADA2基因突变的携带率约1/171,推测中国人群的DADA2患病率约1/116964。展开更多
文摘The crystal and molecular structure of the title complex, Cu（ada）2（py）2（H2O）（ada=adamantanecarboxylic group, py=pyridine）, C 32H 42CuN2O5, were determined by XRD. It belongs to monoclinic system with space group P21/n and crystal cell parameters:a=1.619 9（3）, b=0.680 5（1）, c=2.802 8（6） nm, β=94.15（3）°; V=3.082（1） nm 3, Z=4, Dc=1.289 g/cm3, Mr=589.22, μ（MoKα）=0.750 mm -1, F（000）=1 268. The structure was refined to R=0.057 8 and wR=0.158 1 for 4 447 observed reflections with I≥2σ（I）. The aquo complex is mononuclear with distorted square-pyramidal coordination.
基金supported by Guangzhou Women and Children’s Hospital,Guangzhou Science and Technology Project(No.202201011494 to Liang Dong),and a grant(No.256053 to Andrey V.Zavialov)from the Finnish Academy.
文摘Adenosine,a critical molecule regulating cellular function both inside and outside cells,is controlled by two human adenosine deaminases:ADA1 and ADA2.While ADA1 primarily resides in the cytoplasm,ADA2 can be transported to lysosomes within cells or secreted outside the cell.Patients with ADA2 deficiency(DADA2)often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood.Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages.Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages,and its intracellular concentration decreases in cells secreting TNF-α.This suggests that ADA2 may function as a lysosomal adenosine deaminase,regulating TNF-α expression by the cells.Interestingly,pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage(BAL),correlating with elevated pro-inflammatory cytokine levels.Conversely,cord blood has low ADA2 levels,creating a more immunosuppressive environment.Additionally,secreted ADA2 can bind to apoptotic cells,activating immune cells by reducing extracellular adenosine levels.These findings imply that ADA2 release from monocytes during inflammation,triggered by growth factors,may be crucial for cell activation.Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
