The copper(II) adduct of the unstructured region of the amyloidogenic fragment derived from the human prion protein is redox-active at physiological pH.
The copper(II) adduct of the unstructured region of the amyloidogenic fragment derived from the human prion protein is redox-active at physiological pH.
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源自人朊病毒蛋白的淀粉样蛋白生成片段的非结构化区域的铜(II)加合物在生理pH下具有氧化还原活性。
DOI：
10.1021/ic061236s
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发表时间：
2007
影响因子：
4.6
通讯作者：
P. Soh
中科院分区：
文献类型：
--
作者：
J. Shearer;P. Soh
朊病毒疾病是由朊蛋白（PrP）的错误折叠和聚集引起的。在此，我们提供的证据表明，人类PrP（PrP(91-126)）的非结构化淀粉样蛋白片段的CuII加合物在生理条件下具有氧化还原活性。我们已经确定PrP的相关高亲和力CuII结合区（91-126）包含在残基106和114之间。[CuII(PrP(91-126))]和[CuII(PrP(106-114))]的CuII Kd值约为90微米。此外，较小的PrP片段PrP（106-114）与CuII配位，产生与[CuII(PrP(91-126))]几乎相同的电子吸收光谱（λ max约610 nm (epsilon约125 M-1 cm-1)），表明CuII具有类似的配位环境。Cu K-edge x射线吸收光谱（XAS）显示，这两种金属肽具有几乎相同的昆（N/O）2S配位环境（2N/O约1.97 a， 1S约2.30 a， 1咪唑N约1.95 a）。两者都显示出准可逆的CuII/CuI氧化还原对，相对于Ag/AgCl约为-350 mV。ESI-MS表明，这两种多肽都能协调CuI。然而，XAS表明[CuI(PrP(91-126))]和[CuI(PrP(106-114))]之间的协调环境存在差异。这些数据表明，[CuI(PrP(91-126))]在四坐标（N/O）2S2环境中含有Cu，且(N/O)-Cu键距离相似(Cu-(N/O) r = 2.048(4) a)，而[CuI(PrP(106-114))]在四坐标（N/O）2S2环境中含有Cu，但(N/O)-Cu键距离不同(Cu-(N/O) r1 = 2.057(6) a)；r2 = 2.159(3) A)。尽管配位环境不同，但两种铜金属肽都能以相似的速率催化O2还原为O2*-。
Prion diseases are caused by the misfolding and aggregation of the prion protein (PrP). Herein we provide evidence that the CuII adduct of the unstructured amyloidogenic fragment of the human PrP (PrP(91-126)) is redox active under physiological conditions. We have identified that the relevant high-affinity CuII binding region of PrP(91-126) is contained between residues 106 and 114. Both [CuII(PrP(91-126))] and [CuII(PrP(106-114))] have CuII Kd values of approximately 90 microM. Furthermore, the smaller PrP fragment PrP(106-114) coordinates CuII producing an electronic absorption spectrum nearly identical with [CuII(PrP(91-126))] (lambda max approximately 610 nm (epsilon approximately 125 M-1 cm-1)) suggesting a similar coordination environment for CuII. Cu K-edge X-ray absorption spectroscopy (XAS) reveals a nearly identical CuN(N/O)2S coordination environment for these two metallopeptides (2N/O at approximately 1.97 A; 1S at approximately 2.30 A; 1 imidazole N at approximately 1.95 A). Both display quasireversible CuII/CuI redox couples at approximately -350 mV vs Ag/AgCl. ESI-MS indicates that both peptides will coordinate CuI. However, XAS indicates differential coordination environments between [CuI(PrP(91-126))] and [CuI(PrP(106-114))]. These data indicate that [CuI(PrP(91-126))] contains Cu in a four coordinate (N/O)2S2 environment with similar (N/O)-Cu bond distances (Cu-(N/O) r = 2.048(4) A), while [CuI(PrP(106-114))] contains Cu in a four coordinate (N/O)2S2 environment with differential (N/O)-Cu bond distances (Cu-(N/O) r1 = 2.057(6) A; r2 = 2.159(3) A). Despite the differential coordination environments both Cu-metallopeptides will catalytically reduce O2 to O2*- at comparable rates.
影响因子：
2.9
作者：
Burns, CS;Aronoff-Spencer, E;Millhauser, GL
通讯作者：
Millhauser, GL
DOI：
10.1073/pnas.96.5.2042
发表时间：
1999-03
影响因子：
11.1
作者：
J. H. Viles;F. Cohen;S. Prusiner;D. Goodin;P. Wright;H. Dyson
通讯作者：
J. H. Viles;F. Cohen;S. Prusiner;D. Goodin;P. Wright;H. Dyson
影响因子：
2.9
作者：
Bocharova, OV;Breydo, L;Baskakov, IV
通讯作者：
Baskakov, IV