3ZM6

CRYSTAL STRUCTURE OF MURF LIGASE IN COMPLEX WITH CYANOTHIOPHENE INHIBITOR

3ZM6 の概要

• エントリーDOI: 10.2210/pdb3zm6/pdb
• 関連するPDBエントリー: 3ZL8 3ZM5
• 分子名称: UDP-N-ACETYLMURAMOYL-TRIPEPTIDE--D-ALANYL-D-ALANINE LIGASE, N-(6-(4-(2h-tetrazol-5-yl)benzyl)-3-cyano-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)-2,4-dichloro-5-(morpholinosulfonyl)benzamide (3 entities in total)
• 機能のキーワード: ligase, peptidoglycan synthesis, adp-forming enzyme, cell wall, cell shape, cell cycle, cell divison, nucleotide-binding, atp-binding
• 由来する生物種: STREPTOCOCCUS PNEUMONIAE
• 細胞内の位置: Cytoplasm (By similarity): Q8DNV6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52289.97

構造登録者

Hrast, M.,Turk, S.,Sosic, I.,Knez, D.,Randall, C.P.,Barreteau, H.,Contreras-Martel, C.,Dessen, A.,ONeill, A.J.,Mengin-Lecreulx, D.,Blanot, D.,Gobec, S. (登録日: 2013-02-05, 公開日: 2013-07-03, 最終更新日: 2023-12-20)

主引用文献

Hrast, M.,Turk, S.,Sosic, I.,Knez, D.,Randall, C.P.,Barreteau, H.,Contreras-Martel, C.,Dessen, A.,O'Neill, A.J.,Mengin-Lecreulx, D.,Blanot, D.,Gobec, S.
Structure-Activity Relationships of New Cyanothiophene Inhibitors of the Essential Peptidoglycan Biosynthesis Enzyme Murf.
Eur.J.Med.Chem., 66C:32-, 2013

PubMed Abstract: Peptidoglycan is an essential component of the bacterial cell wall, and enzymes involved in its biosynthesis represent validated targets for antibacterial drug discovery. MurF catalyzes the final intracellular peptidoglycan biosynthesis step: the addition of D-Ala-D-Ala to the nucleotide precursor UDP-MurNAc-L-Ala-γ-D-Glu-meso-DAP (or L-Lys). As MurF has no human counterpart, it represents an attractive target for the development of new antibacterial drugs. Using recently published cyanothiophene inhibitors of MurF from Streptococcus pneumoniae as a starting point, we designed and synthesized a series of structurally related derivatives and investigated their inhibition of MurF enzymes from different bacterial species. Systematic structural modifications of the parent compounds resulted in a series of nanomolar inhibitors of MurF from S. pneumoniae and micromolar inhibitors of MurF from Escherichia coli and Staphylococcus aureus. Some of the inhibitors also show antibacterial activity against S. pneumoniae R6. These findings, together with two new co-crystal structures, represent an excellent starting point for further optimization toward effective novel antibacterials.

PubMed: 23786712
DOI: 10.1016/J.EJMECH.2013.05.013

実験手法

X-RAY DIFFRACTION (1.84 Å)