In response to our recent publication describing affinity-enhanced, long−half-life ACE2-based receptor traps for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralization (1), Liu et al. (2) point to their parallel work showing substrate-dependent peptidase activity of ACE2 active site mutants (3). Understanding the physiologically relevant ACE2 peptidase activity determinants is critical, as several groups are developing ACE2-based receptor traps with intact (4, 5), modestly attenuated (6), or ablated activity (1, 7, 8) to separate the effects of blocking on angiotensin II (Ang II) conversion. Toward this end, we introduced an H345L mutation that is postulated to form part of the oxyanion binding site (9); mutations in the oxyanion hole for zinc metalloproteases (10) are well known to disrupt the tetrahedral oxyanion in the transition state and dramatically …

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回复Liu等人：特定突变对ACE2的特异性和催化作用很重要[生物科学]

针对我们最近发表的文章，描述了用于中和严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的亲和力增强、半衰期长的 ACE2 受体陷阱 ( 1 )，Liu 等人。( 2 ) 指出他们的平行工作显示了 ACE2 活性位点突变体的底物依赖性肽酶活性 ( 3 )。了解生理相关的 ACE2 肽酶活性决定因素至关重要，因为多个研究小组正在开发基于 ACE2 的受体陷阱，其具有完整的 ( 4 , 5 )、适度减弱 ( 6 ) 或消融的活性 ( 1 , 7 , 8 )，以分离阻断血管紧张素 II (Ang II) 转化。为此，我们引入了 H345L 突变，推测该突变形成氧阴离子结合位点的一部分 ( 9 )；众所周知，锌金属蛋白酶 ( 10 )的氧阴离子孔中的突变会破坏过渡态的四面体氧阴离子，并显着……