Leader David P, Milner-White E James
College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
Curr Res Struct Biol. 2023 Sep 18;6:100105. doi: 10.1016/j.crstbi.2023.100105. eCollection 2023.
The crown bridge loop is hexapeptide motif in which the backbone carbonyl group at position 1 is hydrogen bonded to the backbone imino groups of positions 4 and 6. Residues at positions 1 and 4-6 are held in a tight substructure, but different orientations of the plane of the peptide bond between positions 2 and 3 result in two conformers: the 2,3-αα crown bridge loop - found in approximately 7% of proteins - and the 2,3-βα crown bridge loop, found in approximately 1-2% of proteins. We constructed a relational database in which we identified 60 instances of the 2,3-βα conformer, and find that about half occur in enzymes of the haloacid dehalogenase (HAD) superfamily, where they are located next to the catalytic aspartate residue. Analysis of additional enzymes of the HAD superfamily in the extensive SCOPe dataset showed this crown bridge loop to be a conserved feature. Examination of available structures showed that the 2,3-βα conformation - but not the 2,3-αα conformation - allows the backbone carbonyl group at position 2 to interact with the essential Mg ion. The possibility of interconversion between the 2,3-βα and 2,3-αα conformations during catalysis is discussed.
冠桥环是一种六肽基序，其中第1位的主链羰基与第4位和第6位的主链亚氨基形成氢键。第1位以及第4 - 6位的残基形成一个紧密的亚结构，但第2位和第3位之间肽键平面的不同取向导致了两种构象：2,3-αα冠桥环（约7%的蛋白质中存在）和2,3-βα冠桥环（约1 - 2%的蛋白质中存在）。我们构建了一个关系数据库，在其中识别出60个2,3-βα构象的实例，并发现约一半出现在卤代酸脱卤酶（HAD）超家族的酶中，它们位于催化天冬氨酸残基旁边。对广泛的SCOPe数据集中HAD超家族的其他酶进行分析表明，这种冠桥环是一个保守特征。对现有结构的研究表明，2,3-βα构象（而非2,3-αα构象）能使第2位的主链羰基与必需的镁离子相互作用。文中还讨论了催化过程中2,3-βα和2,3-αα构象之间相互转换的可能性。
