2n8j
From Proteopedia
Structure and 15N relaxation data of Calmodulin bound to the endothelial Nitric Oxide Synthase Calmodulin Binding Domain Peptide at Physiological Calcium Concentration
Structural highlights
DiseaseCALM1_HUMAN The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14. FunctionCALM1_HUMAN Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).[1] [2] [3] [4] Publication Abstract from PubMedThe small acidic protein Calmodulin (CaM) serves as a Ca2+ sensor and control element for many enzymes including nitric oxide synthase (NOS) enzymes that play major roles in key physiological and pathological processes. CaM binding causes a conformational change in NOS to allow for the electron transfer between the reductase and oxygenase domains through a process that is thought to be highly dynamic. In this report, NMR spectroscopy was used to determine the solution structure of the endothelial NOS (eNOS) peptide in complex with CaM at the lowest Ca2+ concentration (225 nM) required for CaM to bind to eNOS and corresponds to a physiological elevated Ca2+ level found in mammalian cells. Under these conditions, the CaM-eNOS complex has a Ca2+-replete C-terminal lobe bound the eNOS peptide and a Ca2+ free N-terminal lobe loosely associated to the eNOS peptide. With increasing Ca2+ concentration, the binding of Ca2+ by the N-lobe of CaM results in a stronger interaction with the C-terminal region of the eNOS peptide and increased alpha-helical structure of the peptide that may be part of the mechanism resulting in electron transfer from the FMN to the heme in the oxygenase domain of the enzyme. SPR studies performed under the same conditions show Ca2+ concentration dependent binding kinetics were consistent with the NMR structural results. This investigation shows that structural studies performed under more physiological relevant conditions provide information on subtle changes in structure that may not be apparent when experiments are performed in excess Ca2+ concentrations. Structural Studies of a Complex Between Endothelial Nitric Oxide Synthase and Calmodulin at Physiological Calcium Concentration.,Piazza M, Dieckmann T, Guillemette JG Biochemistry. 2016 Oct 4. PMID:27696828[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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