6GHV

Structure of a DC-SIGN CRD in complex with high affinity glycomimetic.

Summary for 6GHV

• Entry DOI: 10.2210/pdb6ghv/pdb
• Descriptor: CD209 antigen, [1-[(2~{S},3~{S},4~{R},5~{S},6~{R})-2-[(1~{S},2~{S},4~{S},5~{S})-2-(2-chloroethyloxy)-4,5-bis[[4-(hydroxymethyl)phenyl]methylcarbamoyl]cyclohexyl]oxy-6-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-3-yl]-1,2,3-triazol-4-yl]methylazanium, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: dc-sign, inhibitor, sugar binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 112186.70

Authors

Thepaut, M.,Achilli, S.,Medve, L.,Bernardi, A.,Fieschi, F. (deposition date: 2018-05-09, release date: 2019-09-11, Last modification date: 2024-11-06)

Primary citation

Medve, L.,Achilli, S.,Guzman-Caldentey, J.,Thepaut, M.,Senaldi, L.,Le Roy, A.,Sattin, S.,Ebel, C.,Vives, C.,Martin-Santamaria, S.,Bernardi, A.,Fieschi, F.
Enhancing Potency and Selectivity of a DC-SIGN Glycomimetic Ligand by Fragment-Based Design: Structural Basis.
Chemistry, 25:14659-14668, 2019

PubMed Abstract: Chemical modification of pseudo-dimannoside ligands guided by fragment-based design allowed for the exploitation of an ammonium-binding region in the vicinity of the mannose-binding site of DC-SIGN, leading to the synthesis of a glycomimetic antagonist (compound 16) of unprecedented affinity and selectivity against the related lectin langerin. Here, the computational design of pseudo-dimannoside derivatives as DC-SIGN ligands, their synthesis, their evaluation as DC-SIGN selective antagonists, the biophysical characterization of the DC-SIGN/16 complex, and the structural basis for the ligand activity are presented. On the way to the characterization of this ligand, an unusual bridging interaction within the crystals shed light on the plasticity and potential secondary binding sites within the DC-SIGN carbohydrate recognition domain.

PubMed: 31469191
DOI: 10.1002/chem.201903391

Experimental method

X-RAY DIFFRACTION (2.1 Å)