Calcium binding proteins calmodulin

Small ubiquitous calcium-binding protein. Calmodulin binds and regulates the activity of many protein targets involved in cellular signal transduction pathways mediated by calcium. Calmodulin is ranked among the most conserved proteins and plays a key role in many cellular processes. 

It has been shown that the activity of NO synthases is regulated by cofactors calcium binding protein calmodulin and tetrahydrobiopterin (H4B). Abu-Soud et al. [149] have studied the effect of H4B on the activity of neuronal nNOS I, using the isolated heme-containing oxygenase domain nNOSoxy. It was found that nNOSoxy rapidly formed an oxygenated complex in the reaction with dioxygen, which dissociated to produce superoxide (Reaction (6)) ... 

Hathaway, D.R. Adelstein, R.S. Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity. Proc. Natl. Acad. Sci. USA, 76, 1653-1657 (1979)... 

Phosphorylase kinase is one of the best characterized enzyme systems to illustrate the role of calcium ions in regulation of intermediary metabolism. Phosphorylase kinase is composed of four different subunits termed a (Mr 145000), /3 (MT 128000), y (A/r 45000) and 5 (Mr 17000) and has the structure (a/3y8)A [106]. Only one of its four subunits actually catalyses the phosphorylation reaction the other three subunits are regulatory and enable the enzyme complex to be activated both by calcium and cyclic AMP. The y subunit carries the catalytic activity the 8 subunit is the calcium binding protein calmodulin and is responsible for the calcium dependence of the enzyme. The a and /3 subunits are the targets for cyclic-AMP mediated regulation, both being phosphorylated by the cyclic-AMP dependent protein kinase. Calmodulin appears to interact with phosphorylase kinase in a different manner from other enzymes, since it is an integral component of the enzyme. Phosphorylase kinase has an absolute requirement for calcium, and is inactive in its absence. 

Most opiates act through peripheral and central mechanisms with the exception of loperamide, which acts only peripherally. Loperamide is antisecretory it inhibits the calcium-binding protein calmodulin, controlling chloride secretion. Loperamide, available as 2-mg capsules or 1 mg/5 mL solution (both are nonprescription... 

Overall changes in ionic conditions will affect most enzymes, particularly if they have a requirement for the involvement of a particular ion, as in the case of Mg2+ and protein kinases. [Ca2+] has specific effects that are mediated by the calcium-binding protein calmodulin. 

Calcium transport ATPase Calcium binding protein Calmodulin... 

In the PIP2-Ca signal transduction system, the signal is transferred from the epinephrine receptor to membrane-bound phospholipase C by G proteins. Phospholipase C hydrolyzes PIP2 to form diacylglycerol (DAG) and inositol trisphos-phate (IP3). IP3 stimulates the release of Ca from the endoplasmic reticulum. Ca and DAG activate protein kinase C. The amount of calcium bound to one of the calcium-binding proteins, calmodulin, is also increased. 

FIGURE 24.12 The PIP2 second-messenger scheme. When a hormone binds to a receptor, it activates phospholipase C, in a process mediated by a G protein. Phospholipase C hydrolyzes PIPj to IP3 and DAG. IP3 stimulates the release of Ca from intracellular reservoirs in the ER. A complex formed between Ca and the calcium-binding protein calmodulin activates a cytosolic protein kinase for phosphorylation of a target enzyme. DAG remains bound to the plasma membrane, where it activates the membrane-bound protein kinase C (PKC). PKC is involved in the phosphorylation-channel proteins that control the flow of Ca + in and out of the cell. Ca from extracellular sources can produce sustained responses even when the supply of Ca + in intracellular reservoirs is exhausted. 

Figure 1. Three-dimensional structures of the intracellular EF-hand calcium-binding proteins calmodulin (3cln), parvalbumin (5cpv), and calbindinD9k (4icb).

In the biological system, NO is produced by nitric oxide synthase, NOS, which occurs in at least three forms the endothelial form, eNOS, found in endothelial cells the neuronal form, nNOS, found in neural tissues the inducible form, iNOS, found in macrophages. Formation of the latter is triggered by the calcium-binding protein, calmodulin. The NOS enzymes contain iron in a coordination environment like that in cytochrome P-4S0-CAM. The substrate is L-arginine, and the products are NO and citrulline ... 

Other possible mechanisms of pyrethroid toxicity have been investigated. Inhibition of Ca ", Mg -ATPase, and calcium-binding protein calmodulin has been observed with some pyrethroids. 

Keywords alkaline phosphatase calbindin calcium-binding proteins calmodulin metaUothimiein Cd NMR methods Cd NMR chemical shifts from metaUoproteins... 

---