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 cAMP responsive element-binding protein (CREB) is central to second messenger regulated transcription. To elucidate the structural mechanisms of DNA binding and selective dimerization of CREB, we determined to 3.0 A resolution, the structure of the CREB bZIP (residues 283-341) bound to a 21-base pair deoxynucleotide that encompasses the canonical 8-base pair somatostatin cAMP response element (SSCRE). The CREB dimer is stabilized in part by ionic interactions from Arg(314) to Glu(319') and Glu(328) to Lys(333') as well as a hydrogen bond network that links the carboxamide side chains of Gln(322')-Asn(321)-Asn(321')-Gln(322). Critical to family selective dimerization are intersubunit hydrogen bonds between basic region residue Tyr(307) and leucine zipper residue Glu(312), which are conserved in all CREB/CREM/ATF-1 family members. Strikingly, the structure reveals a hexahydrated Mg(2+) ion bound in the cavity between the basic region and SSCRE that makes a water-mediated DNA contact. DNA binding studies demonstrate that Mg(2+) ions enhance CREB bZIP:SSCRE binding by more than 25-fold and suggest a possible physiological role for this ion in somatostatin cAMP response element and potentially other CRE-mediated gene expression.
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PMID:The structure of a CREB bZIP.somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding. 1095 92

In some individuals, the consumption of coffee beverages is related to symptoms of gastric irritation. Hot water steam-treatment of raw coffee beans is hypothesized to reduce the contents of stomach irritating compounds, and products to which this technology is applied are launched as stomach-friendly coffee. However, data on the effect of steam-treated coffee on gastric acid secretion are conflicting and it has not been proven yet as to which coffee components act as pro- or antisecretory stimulants. The work presented here aimed at the characterization of a coffee beverage that effectively down-regulates mechanisms of proton secretion in human gastric cells (HGT-1). At first, a regular coffee beverage was fractionated by using solvents of different polarity: water, ethylacetate, dichloromethane, and pentane. Functional assays on the proton secretory activity (PSA) of these solvent fractions revealed the least pronounced effect for the water fraction, for which quantitative analyses demonstrated the highest distribution of chlorogenic acid (95%), (beta)N-alkanoyl-5-hydroxytryptamides (55%), and N-methylpyridinium (N-MP, >99%) among all fractions. Following experiments demonstrated that HGT-1 cells treated with regular coffee fortified with N-MP at a concentration of about 20 mg/mL N-MP showed a significantly decreased PSA as compared to cells which were exposed to coffee beverages containing higher (32-34 mg/L) or lower (5 mg/L) N-MP concentrations. Results from cellular pathway analyses of transcription (ATF-1 and Akt1) and signaling (cAMP and EGFr) factors and kinases (ERK1/2), and experiments on the gene expression of pro (histamine-HRH2 and acetylcholine-CHRM3)- and anti (somatostatin-SSTR1)-secretory receptors and H(+),K(+)-ATPase verified this antisecretory activity of N-MP in coffee beverages.
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PMID:Activity-guided fractionation to characterize a coffee beverage that effectively down-regulates mechanisms of gastric acid secretion as compared to regular coffee. 2023 36