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1.
Conantokin-T (con-T) and conantokin-G (con-G) are two highly homologous peptide toxins found in Conus venom. The former is a 21-residue peptide with four gamma-carboxyglutamic acid (Gla) residues (at positions 3, 4, 10 and 14), while the latter is a 17-residue peptide with five gamma-carboxyglutamic acid residues (at positions 3, 4, 7, 10 and 14). Despite the apparent similarity in number and relative positions of the gamma-carboxyglutamic acid residues, (113)Cd-NMR studies indicated a distinct metal binding behavior for con-G and con-T. There appears to be four binding sites in con-G in contrast to one metal binding site in con-T. To elucidate the mode of calcium binding by the gamma-carboxyglutamic acid residues in these conantokins, we designed various analogous peptides with their gamma-carboxyglutamic acid replaced by other amino acid residues. (113)Cd-NMR experiments on conantokin analogues reveal that the major difference in the number of metal binding sites between con-G and con-T is due to the residue at position 7. We also performed molecular simulations to calculate the relative binding free energies of several potential binding sites. Based on our theoretical and experimental results, we propose a 'four-site' binding model for conantokin-G and a 'single-site' binding model for conantokin-T. 相似文献
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Cd2+ provokes inositol trisphosphateproduction and releases stored Ca2+, apparently by binding to a zinc site in the external domain of an orphan receptor. One pM Cd2+ evokes an immediate spike in cytosolic free Ca2+, which is similar to that evoked by bradykinin. Platelet-derived growth factor (PDGF) also increases free Ca2+ in human dermalfibroblasts, but there is a distinct lag before free Ca2+ rises in response to PDGF. Genistein, which selectively inhibits tyrosine kinases, markedly inhibited Ca2+ mobilization evoked by PDGF. Calcium mobilization triggered by cadmium or bradykinin was relatively insensitive to genistein. The PDGF receptor is known to be a tyrosine kinase, whichphosphorylates and thereby activatesphospholipase C, whereas a G protein couples the bradykinin receptor to anotherphospholipase C isoform. These findings support the hypothesis that the orphan receptor triggered by cadmium is coupled to phospholipase C via a G protein.Abbreviations BSA
bovine serum albumin
- BK
bradykinin
- [Ca2+]i
cytosolic free calcium
- DME
Dulbecco's modified Eagle's medium
- FBS
fetal bovine serum
- HEPES
4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid
- IC50
concentration that produces 50% inhibition
- PDGF
platelet-derived growth factor
- PSS
physiological salts solution
- SE
standard error of the mean 相似文献
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报道了在海南热带雨林国家公园内发现的兰科牛齿兰属中国一新记录种:广椭牛齿兰[Appendicula ovalis(Schltr.) J.J.Sm. ex Mansf.]。该种原分布于马来半岛、苏门答腊岛、爪哇岛、婆罗洲、苏拉威西岛,在形态上与国内记录的4种牛齿兰属植物均有较大差别,如茎中部具分枝、叶广椭圆形、单个花序仅着生1朵花、且唇瓣扭转具粉紫色斑块等特征。对产自海南的该种形态和生境进行了详细描述,并提供高清解剖照片。凭证标本保存于海南大学林学院教学标本馆(HUFB)。 相似文献
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