5A5F

CRYSTAL STRUCTURE OF MURD LIGASE FROM ESCHERICHIA COLI IN COMPLEX WITH UMA AND ADP

5A5F の概要

• エントリーDOI: 10.2210/pdb5a5f/pdb
• 関連するPDBエントリー: 5A5E
• 分子名称: UDP-N-ACETYLMURAMOYLALANINE--D-GLUTAMATE LIGASE, URIDINE-5'-DIPHOSPHATE-N-ACETYLMURAMOYL-L-ALANINE, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: ligase, peptidoglycan synthesis, adp-forming enzyme, cell wall, cell shape, cell cycle, nucleotide-binding, atp- binding, cell division, ligand, conformation
• 由来する生物種: Escherichia coli K-12
• 細胞内の位置: Cytoplasm: P14900
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48358.12

構造登録者

Sink, R.,Kotnik, M.,Zega, A.,Barreteau, H.,Gobec, S.,Blanot, D.,Dessen, A.,Contreras-Martel, C. (登録日: 2015-06-17, 公開日: 2016-04-13, 最終更新日: 2024-11-13)

主引用文献

Sink, R.,Kotnik, M.,Zega, A.,Barreteau, H.,Gobec, S.,Blanot, D.,Dessen, A.,Contreras-Martel, C.
Crystallographic Study of Peptidoglycan Biosynthesis Enzyme MurD: Domain Movement Revisited.
PLoS ONE, 11:e0152075-e0152075, 2016

PubMed Abstract: The biosynthetic pathway of peptidoglycan, an essential component of bacterial cell wall, is a well-recognized target for antibiotic development. Peptidoglycan precursors are synthesized in the bacterial cytosol by various enzymes including the ATP-hydrolyzing Mur ligases, which catalyze the stepwise addition of amino acids to a UDP-MurNAc precursor to yield UDP-MurNAc-pentapeptide. MurD catalyzes the addition of D-glutamic acid to UDP-MurNAc-L-Ala in the presence of ATP; structural and biochemical studies have suggested the binding of the substrates with an ordered kinetic mechanism in which ligand binding inevitably closes the active site. In this work, we challenge this assumption by reporting the crystal structures of intermediate forms of MurD either in the absence of ligands or in the presence of small molecules. A detailed analysis provides insight into the events that lead to the closure of MurD and reveals that minor structural modifications contribute to major overall conformation alterations. These novel insights will be instrumental in the development of new potential antibiotics designed to target the peptidoglycan biosynthetic pathway.

PubMed: 27031227
DOI: 10.1371/journal.pone.0152075

実験手法

X-RAY DIFFRACTION (1.9 Å)