Tu Xiongying, Latham John A, Klema Valerie J, Evans Robert L, Li Chao, Klinman Judith P, Wilmot Carrie M
Department of Biochemistry, Molecular Biology, and Biophysics, and The Biotechnology Institute, University of Minnesota, St Paul, MN, 55108, USA.
Departments of Chemistry, and Molecular and Cellular Biology, University of California, Berkeley, CA, 94720, USA.
J Biol Inorg Chem. 2017 Oct;22(7):1089-1097. doi: 10.1007/s00775-017-1486-8. Epub 2017 Aug 19.
PqqB is an enzyme involved in the biosynthesis of pyrroloquinoline quinone and a distal member of the metallo-β-lactamase (MBL) superfamily. PqqB lacks two residues in the conserved signature motif HxHxDH that makes up the key metal-chelating elements that can bind up to two metal ions at the active site of MBLs and other members of its superfamily. Here, we report crystal structures of PqqB bound to Mn, Mg, Cu, and Zn. These structures demonstrate that PqqB can still bind metal ions at the canonical MBL active site. The fact that PqqB can adapt its side chains to chelate a wide spectrum of metal ions with different coordination features on a uniform main chain scaffold demonstrates its metal-binding plasticity. This plasticity may provide insights into the structural basis of promiscuous activities found in ensembles of metal complexes within this superfamily. Furthermore, PqqB belongs to a small subclass of MBLs that contain an additional CxCxxC motif that binds a structural Zn. Our data support a key role for this motif in dimerization.
PqqB是一种参与吡咯喹啉醌生物合成的酶，属于金属β-内酰胺酶（MBL）超家族的远亲成员。PqqB在保守的特征基序HxHxDH中缺少两个残基，该基序构成了关键的金属螯合元件，能够在MBL及其超家族其他成员的活性位点结合多达两个金属离子。在此，我们报告了结合锰、镁、铜和锌的PqqB的晶体结构。这些结构表明，PqqB仍能在典型的MBL活性位点结合金属离子。PqqB能够在统一的主链支架上通过调整其侧链来螯合具有不同配位特征的多种金属离子，这一事实证明了其金属结合可塑性。这种可塑性可能为深入了解该超家族中金属配合物组合中杂乱活性的结构基础提供线索。此外，PqqB属于MBL的一个小亚类，包含一个额外的结合结构锌的CxCxxC基序。我们的数据支持该基序在二聚化中起关键作用。
