Stasyuk Anastasiya, Smith Clyde A
Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA.
Department of Chemistry, Stanford University, Stanford, CA.
bioRxiv. 2025 Jan 22:2025.01.20.633977. doi: 10.1101/2025.01.20.633977.
Over 1370 class D β-lactamases are currently known, and they pose a serious threat to the effective treatment of many infectious diseases, particularly in some pathogenic bacteria where evolving carbapenemase activity has been reported. Detailed understanding of their molecular biology, enzymology and structural biology are critically important but the lack of a standardized residue numbering scheme and inconsistent secondary structure annotation has made comparative analyses sometimes difficult and cumbersome. Compounding this, in the post-AlphaFold world where we currently find ourselves, an extraordinary wealth of detailed structural information on these enzymes is literally at our fingertips, therefore it is vitally important that a standard numbering system is in place to facilitate the accurate and straightforward analysis of their structures. Here we present a residue numbering and secondary structure scheme for the class D enzymes and apply it to test targets to demonstrate ease at which it can be used.
目前已知超过1370种D类β-内酰胺酶，它们对许多传染病的有效治疗构成严重威胁，特别是在一些已报道出现碳青霉烯酶活性演变的病原菌中。深入了解它们的分子生物学、酶学和结构生物学至关重要，但缺乏标准化的残基编号方案以及二级结构注释不一致，有时会使比较分析变得困难和繁琐。更复杂的是，在我们当前所处的AlphaFold时代之后，关于这些酶的大量详细结构信息触手可及，因此建立一个标准编号系统对于促进对其结构进行准确和直接的分析至关重要。在这里，我们提出了一种D类酶的残基编号和二级结构方案，并将其应用于测试靶点，以证明其使用的简便性。
