i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal.
IBMC - Instituto de Biologia Molecular e Celular Universidade do Porto, Portugal.
FEBS Lett. 2019 Jan;593(1):128-137. doi: 10.1002/1873-3468.13285. Epub 2018 Nov 23.
The interaction of the amyloid-β peptide (Aβ) with thermolysin (TLN) was investigated by X-ray crystallography. Structural models of the complexes of TLN with several Aβ fragments show that, despite the numerous possible cleavage sites of the Aβ sequence, the C-terminal product of Ala30-Ile31 cleavage does not dissociate, thus inhibiting the enzyme. The high similarity between the TLN structural motif and neprilysin (NEP), the most extensively studied peptidase associated with Aβ clearance, suggests that NEP should be more efficient against Aβ polymorphs where Ala30-Ile31 is inaccessible, which is in agreement with studies in living mice that point to the limited role of NEP in degrading soluble Aβ and its higher ability to degrade insoluble and/or oligomeric Aβ forms, producing only the Aβ intermediate.
通过 X 射线晶体学研究了淀粉样β肽 (Aβ) 与组织蛋白酶 L (TLN) 的相互作用。TLN 与几个 Aβ 片段复合物的结构模型表明，尽管 Aβ 序列有许多可能的切割位点，但 Ala30-Ile31 切割的 C 末端产物不会解离，从而抑制了酶的活性。TLN 结构基序与 Neprilysin（NEP）高度相似，NEP 是与 Aβ 清除相关的研究最广泛的肽酶之一，这表明 NEP 应该更有效地针对 Ala30-Ile31 不可及的 Aβ 多态体，这与活体小鼠研究结果一致，这些研究表明 NEP 在降解可溶性 Aβ 方面的作用有限，而其降解不溶性和/或寡聚 Aβ 形式的能力较高，只会产生 Aβ 中间产物。
