PfSERA5, a significantly abundant protein present within the parasitophorous vacuole (PV) and essential for normal growth during the blood‐stage life cycle of the malaria parasite Plasmodium falciparum, displays structural similarity to many other cysteine proteases. However, PfSERA5 does not exhibit any detectable protease activity and therefore the role of the PfSERA5 papain‐like domain (PfSERA5E), thought to remain bound to its cognate prodomain, remains unknown. In this study, we present a revised structure of the central PfSERA5E domain at a resolution of 1.2 Å, and the first structure of the “zymogen” of this papain‐like domain including its cognate prodomain (PfSERA5PE) to 2.2 Å resolution. PfSERA5PE is somewhat structurally similar to that of other known proenzymes, retaining the conserved overall folding and orientation of the prodomain through, and occluding, the archetypal papain‐like catalytic triad “active‐site” cleft, in the same reverse direction as conventional prodomains. Our findings are congruent with previously identified structures of PfSERA5E and of similar “zymogens” and provide a foundation for further investigation into the function of PfSERA5.

中文翻译：

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恶性疟原虫 PfSERA5 假酶原的结构。

PfSERA5 是一种存在于寄生液泡 (PV) 中的蛋白质，对于疟原虫恶性疟原虫血液阶段生命周期中的正常生长至关重要，它与许多其他半胱氨酸蛋白酶表现出结构相似性。然而，PfSERA5 不表现出任何可检测的蛋白酶活性，因此 PfSERA5 木瓜蛋白酶样结构域 (PfSERA5E)（被认为与其同源前结构域保持结合）的作用仍然未知。在本研究中，我们以 1.2 Å 的分辨率展示了中央 PfSERA5E 结构域的修订结构，以及该木瓜蛋白酶样结构域的“酶原”的第一个结构，包括其同源前结构域 (PfSERA5PE)，分辨率为 2.2 Å。PfSERA5PE在结构上与其他已知的酶原有些相似，保留了前结构域的保守整体折叠和方向，并封闭了原型木瓜蛋白酶样催化三联体“活性位点”裂口，与传统前结构域的相反方向相同。我们的研究结果与先前确定的 PfSERA5E 和类似“酶原”的结构一致，并为进一步研究 PfSERA5 的功能奠定了基础。