Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of the cyclic peptide (+)-D-Phe1-Cys2-Phe3-D-Trp4-(+)-Lys5-Thr6- Cys7-Thr(ol)8, a somatostatin analogue (SMS 201-995), and the potential-sensitive dye 2-(p-toluidinyl)naphthalene-6-sulfonate (TNS) to lipid membranes was investigated with high-sensitivity titration calorimetry. The binding enthalpy of the peptide was found to vary dramatically with the vesicle size. For highly curved vesicles with a diameter of d congruent to 30 nm, the binding reaction was enthalpy-driven with delta H congruent to -7.0 +/- 0.3 kcal/mol; for large vesicles with more tightly packed lipids, the binding reaction became endothermic with delta H congruent to +1.0 +/- 0.3 kcal/mol and was entropy-driven. In contrast, the free energy of binding was almost independent of the vesicle size. The thermodynamic analysis suggests that the observed enthalpy-entropy compensation of about 8 kcal/mol can be related to a change in the internal tension of the bilayer and is brought about by an entropy increase of the lipid matrix. The "entropy potential" of the membrane may have its molecular origin in the excitation of the hydrocarbon chains to a more disordered configuration and may play a more important role in membrane partition equilibria than the classical hydrophobic effect. The binding of the peptide to the membrane surface induced a pK shift of the peptide terminal amino group. Neutral membranes were found to destabilize the NH3+ group, leading to a decrease in pK; negatively charged membranes, generated an apparent increase in pK due to the increase in proton concentration near the membrane surface. No pK shifts were seen for TNS. Titration calorimetry combined with the Gouy-Chapman theory can be used to determine both the reaction enthalpy and the binding constant of the membrane-binding equilibrium.
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PMID:Peptide binding to lipid bilayers. Nonclassical hydrophobic effect and membrane-induced pK shifts. 139 Jul 63

Pituitary GH secretion is regulated by Ca+2 and cAMP. We show that human pancreatic tumor GRF (hpGRF) stimulates anterior pituitary adenylate cyclase activity, cAMP accumulation, and GH release. The relationship between Ca+2 and the stimulating effects of the Ca+2 ionophore A23187 on cAMP accumulation and GH release in vitro was studied. To evaluate the role of the Ca+2-binding protein calmodulin in this system, we used the calmodulin antagonist W7, a naphthalene-sulfonamide derivative, and its less active analog W5. W7 inhibited hpGRF-stimulated adenylate cyclase activity, cAMP accumulation, and GH release, whereas W5 was either poorly effective or ineffective. Somatostatin (SRIF) also attenuated hpGRF stimulation of adenylate cyclase. These results suggest that the actions of Ca+2-calmodulin and cAMP are interrelated in modulating GH release. Calmodulin participates in hpGRF stimulation of adenylate cyclase, cAMP formation, and GH release. The attenuation of hpGRF-stimulated adenylate cyclase activity by SRIF may be one of the mechanisms for its GH inhibitory action.
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PMID:Human pancreatic tumor growth hormone-releasing factor stimulates anterior pituitary adenylate cyclase activity, adenosine 3',5'-monophosphate accumulation, and growth hormone release in a calmodulin-dependent manner. 614 31

We have prepared a fluorescent conjugate of porcine calmodulin with 5-(dimethylamino)-1-naphthalene-sulfonyl chloride that is highly sensitive to both calcium binding and protein binding. We have used the fluorescence of this conjugate in addition to the intrinsic peptide fluorescence to show that adrenocorticotropic hormone (ACTH), beta-endorphin, glucagon, and substance P undergo calcium-dependent binding by calmodulin, with competition for common binding sites. The dissociation constants determined in the presence of 0.85 mM CaCl2 and 0.2 N KC1, pH 7.3 at 25 degrees C, range from 1.5 muM to 3.4 muM. The alpha-melanocyte-stimulating hormone, bombesin, and somatostatin also bind, with dissociation constants between 60 muM and 90 muM. Angiotensins I and III, bradykinin, neurotensin, physalaemin, substance P octapeptide, insulin, and Leu- and Met-enkephalin show little or no binding. Sequence comparisons show that the peptides that bind calmodulin well contain regions structurally similar to the recognition sequence for the cAMP-dependent protein kinase and to the sequences surrounding phosphorylated serine residues in several calmodulin binding proteins. This result suggests that modification of calmodulin binding sites in calmodulin-dependent proteins is one of the functions of protein kinase. Calcium has a dual role in peptide binding by calmodulin. The occupation of calcium binding sites having a pK approximately 4 results in a 2-fold increase in peptide binding affinity.
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PMID:Binding of simple peptides, hormones, and neurotransmitters by calmodulin. 618 Jul 61