7A54

Two copies of the catalytic domain of NanA sialidase from Streptococcus pneumoniae juxtaposed in the P212121 space group, in complex with DANA

7A54 の概要

• エントリーDOI: 10.2210/pdb7a54/pdb
• 分子名称: Sialidase A, 2-DEOXY-2,3-DEHYDRO-N-ACETYL-NEURAMINIC ACID (3 entities in total)
• 機能のキーワード: sialidase, catalytic domain, dana, structural protein
• 由来する生物種: Streptococcus pneumoniae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 112865.70

構造登録者

Bridot, C.,Bouckaert, J. (登録日: 2020-08-20, 公開日: 2020-11-18, 最終更新日: 2024-01-31)

主引用文献

Assailly, C.,Bridot, C.,Saumonneau, A.,Lottin, P.,Roubinet, B.,Krammer, E.M.,Francois, F.,Vena, F.,Landemarre, L.,Alvarez Dorta, D.,Deniaud, D.,Grandjean, C.,Tellier, C.,Pascual, S.,Montembault, V.,Fontaine, L.,Daligault, F.,Bouckaert, J.,Gouin, S.G.
Polyvalent Transition-State Analogues of Sialyl Substrates Strongly Inhibit Bacterial Sialidases*.
Chemistry, 27:3142-3150, 2021

PubMed Abstract: Bacterial sialidases (SA) are validated drug targets expressed by common human pathogens such as Streptococcus pneumoniae, Vibrio cholerae, or Clostridium perfringens. Noncovalent inhibitors of bacterial SA capable of reaching the submicromolar level are rarely reported. In this work, multi- and polyvalent compounds are developed, based on the transition-state analogue 2-deoxy-2,3-didehydro-N-acetylneuraminic (DANA). Poly-DANA inhibits the catalytic activity of SA from S. pneumoniae (NanA) and the symbiotic microorganism B. thetaiotaomicron (BtSA) at the picomolar and low nanomolar levels (expressed in moles of molecules and of DANA, respectively). Each DANA grafted to the polymer surpasses the inhibitory potential of the monovalent analogue by more than four orders of magnitude, which represents the highest multivalent effect reported so far for an enzyme inhibition. The synergistic interaction is shown to operate exclusively in the catalytic domain, and not in the flanked carbohydrate-binding module (CBM). These results offer interesting perspectives for the multivalent inhibition of other SA families lacking a CBM, such as viral, parasitic, or human SA.

PubMed: 33150981
DOI: 10.1002/chem.202004672

実験手法

X-RAY DIFFRACTION (2.7 Å)