CALMODULIN TARGET PROTEINS; STRUCTURE FUNCTION RELATIONSHIPS

研究计划包括检查不同的家族 钙调素依赖的酶决定：(1)结构或 功能基序(2)推定的亲水性/疏水性指数 钙调蛋白结合区；(3)磷酸化位点的位置 或假底物结构域或与 钙调蛋白结合域；(4)序列数据库搜索 类似于与钙调蛋白结合相关的区域；(5)次级 钙调蛋白(CAM)结合附近的结构预测 (6)通过点图法检测内部重复序列；(6)检测 通过动态规划程序进行局部多重比对。酶 要调查的序列将包括CAM的整个光谱 靶蛋白。谱图包括：1类靶蛋白， 在没有相关钙离子的情况下与CAM结合，与 Ca2+-CAM；在缺乏钙调素的情况下与CAM强烈结合的第2类蛋白 钙离子和被钙离子正激活的3类蛋白； 对钙调素亲和力高，对类亲和力弱或无亲和力 2是巨噬细胞一氧化氮合酶，肺环3‘，5’-核苷酸 磷酸二酯酶、百日咳杆菌腺苷环化酶和 糖原磷酸化酶b激酶；以及包含剩余的 酶和蛋白质，如钙调神经磷酸酶、肌球蛋白轻链激酶、 钙调蛋白，腺苷环化酶，Fodrin，IP3激酶，Marcks蛋白， 内收蛋白、蛋白激酶、钙离子ATPase泵及相关蛋白。

The research plan involves examining the different families of calmodulin-dependent enzymes to determine: (1) structural or functional motifs (2) hydrophilicity/hydrophobicity index of putative calmodulin-binding regions; (3) the position of phosphorylation sites or pseudosubstrate domains or the homologous regions relative to the calmodulin-binding domain; (4) searching database for sequences similar to regions associated with calmodulin binding; (5) secondary structure prediction in the vicinity of the calmodulin (CAM) binding site; (6) internal repeated sequences via dot plot; (6) examination of local multiple alignments by dynamic programming procedures. Enzyme sequences to be investigated will include the entire spectrum of CAM target proteins. The spectrum includes: Class 1 target proteins that bind to CAM without associated Ca2+ and have little affinity for Ca2+-CAM; Class 2 proteins that bind CAM strongly in the absence of Ca2+ and are positively activated by Ca2+ ; and Class 3 proteins that have high affinity for the CAM-Ca2+ and weak or no affinity for Class 2 are macrophage NO synthases, lung cyclic 3', 5'-nucleotide phosphodiesterase, bordetella pertussis adenylate cyclase, and glycogen phosphorylase b kinase; and class 3 containing the remaining enzymes and proteins such as calcineurin, myosin light chain kinase, caldesmon, adenylate cyclases, fodrin, IP3 kinase, marcks protein, adducins, protein kinases, Ca2+ ATPase pumps and related proteins.