7a5x | pdb_00007a5x

Two copies of the catalytic domain of NanA sialidase from Streptococcus pneumoniae juxtaposed in the P212121 space group, in complex with DANA derivatized with a PEG linker on the glycerol group.

spinqualitylabelsall models 7a5x, resolution 1.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7a5x is a 2 chain structure with sequence from "diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, CL, R7H, SO4 Gene: nanA ("Diplococcus pneumoniae" (Klein 1884) Weichselbaum 1886) Activity: Exo-alpha-sialidase, with EC number 3.2.1.18 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Bacterial sialidases (SA) are validated drug targets expressed by common human pathogens such as Streptococcus pneumoniae, Vibrio cholerae or Clostridium perfringens. Non-covalent inhibitors of bacterial SA capable of reaching the submicromolar level are rarely reported. We developed multi- and polyvalent compounds 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 when 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 was shown to operate in the catalytic domain exclusively, and not in the flanked carbohydrate-binding module (CBM). These results offers interesting perspectives for the multivalent inhibition of other SA families lacking a CBM, such as viral, parasitic or human SA.. Polyvalent transition-state analogues of sialyl substrates strongly inhibit bacterial sialidases.,Assailly C, Bridot C, Saumonneau A, Lottin P, Roubinet B, Krammer EM, 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 SG Chemistry. 2020 Nov 5. doi: 10.1002/chem.202004672. PMID:33150981 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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