Strong and widespread action of site-specific positive selection in the snake venom Kunitz/BPTI protein family.
Strong and widespread action of site-specific positive selection in the snake venom Kunitz/BPTI protein family.
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DOI：
10.1038/srep37054
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发表时间：
2016-11-14
影响因子：
4.6
通讯作者：
Kordiš D
中科院分区：
文献类型：
--
作者：
Župunski V;Kordiš D
丝氨酸肽酶S1家族是最大的肽酶家族。它们被Kunitz/BPTI抑制剂特异性抑制。Kunitz结构域具有紧凑的3D结构，具有抑制S1肽酶的最重要的抑制环。在本研究中，我们分析了位点特异性正选择的作用及其对蛇毒Kunitz/BPTI蛋白家族的结构和功能重要部分的影响。通过使用许多模型，我们证明了存在大量的位点特异性正选择位点，可以达到Kunitz域的30-50%。Kunitz/BPTI抑制剂的3D模型上的正选择位点的映射显示，这些位点位于抑制环1和2中，但也位于Kunitz支架中。氨基酸的替换只在表面上发现，而且绝大多数的替换引起电荷的变化。这些替换的结果是Kunitz/BPTI蛋白表面上的静电势的变化，这可能在这些抑制剂精确靶向丝氨酸肽酶S1家族的活性位点中发挥重要作用。
S1 family of serine peptidases is the largest family of peptidases. They are specifically inhibited by the Kunitz/BPTI inhibitors. Kunitz domain is characterized by the compact 3D structure with the most important inhibitory loops for the inhibition of S1 peptidases. In the present study we analysed the action of site-specific positive selection and its impact on the structurally and functionally important parts of the snake venom Kunitz/BPTI family of proteins. By using numerous models we demonstrated the presence of large numbers of site-specific positively selected sites that can reach between 30–50% of the Kunitz domain. The mapping of the positively selected sites on the 3D model of Kunitz/BPTI inhibitors has shown that these sites are located in the inhibitory loops 1 and 2, but also in the Kunitz scaffold. Amino acid replacements have been found exclusively on the surface, and the vast majority of replacements are causing the change of the charge. The consequence of these replacements is the change in the electrostatic potential on the surface of the Kunitz/BPTI proteins that may play an important role in the precise targeting of these inhibitors into the active site of S1 family of serine peptidases.
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影响因子：
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作者：
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