7BYQ

The mutant variant of PNGM-1. H279A was substituted for alanine to study metal coordination.

7BYQ の概要

• エントリーDOI: 10.2210/pdb7byq/pdb
• 関連するPDBエントリー: 6j4n
• 分子名称: Metallo-beta-lactamase PNGM-1, ZINC ION (3 entities in total)
• 機能のキーワード: rnase z, mbls, zinc binding motif, antibiotic
• 由来する生物種: uncultured bacterium
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 166799.46

構造登録者

Park, Y.S.,Kang, L.W.,Lee, J.H. (登録日: 2020-04-24, 公開日: 2021-04-28, 最終更新日: 2023-11-29)

主引用文献

Park, Y.S.,Kim, T.Y.,Park, H.,Lee, J.H.,Nguyen, D.Q.,Hong, M.K.,Lee, S.H.,Kang, L.W.
Structural Study of Metal Binding and Coordination in Ancient Metallo-beta-Lactamase PNGM-1 Variants.
Int J Mol Sci, 21:-, 2020

PubMed Abstract: The increasing incidence of community- and hospital-acquired infections with multidrug-resistant (MDR) bacteria poses a critical threat to public health and the healthcare system. Although β-lactam antibiotics are effective against most bacterial infections, some bacteria are resistant to β-lactam antibiotics by producing β-lactamases. Among β-lactamases, metallo-β-lactamases (MBLs) are especially worrisome as only a few inhibitors have been developed against them. In MBLs, the metal ions play an important role as they coordinate a catalytic water molecule that hydrolyzes β-lactam rings. We determined the crystal structures of different variants of PNGM-1, an ancient MBL with additional tRNase Z activity. The variants were generated by site-directed mutagenesis targeting metal-coordinating residues. In PNGM-1, both zinc ions are coordinated by six coordination partners in an octahedral geometry, and the zinc-centered octahedrons share a common face. Structures of the PNGM-1 variants confirm that the substitution of a metal-coordinating residue causes the loss of metal binding and β-lactamase activity. Compared with PNGM-1, subclass B3 MBLs lack one metal-coordinating residue, leading to a shift in the metal-coordination geometry from an octahedral to tetrahedral geometry. Our results imply that a subtle change in the metal-binding site of MBLs can markedly change their metal-coordination geometry and catalytic activity.

PubMed: 32664695
DOI: 10.3390/ijms21144926

実験手法

X-RAY DIFFRACTION (1.96 Å)