4LP6

Crystal Structure of Human Carbonic Anhydrase II in complex with a quinoline oligoamide foldamer

Summary for 4LP6

• Entry DOI: 10.2210/pdb4lp6/pdb
• Descriptor: Carbonic anhydrase 2, 8-({[4-(3-aminopropoxy)-8-({[4-hydroxy-8-({[4-(2-methylpropoxy)-8-({[4-(3-{[(4-sulfamoylbenzoyl)amino]methyl}phenoxy)butyl]carbamoyl}amino)quinolin-2-yl]carbonyl}amino)quinolin-2-yl]carbonyl}amino)quinolin-2-yl]carbonyl}amino)-4-(carboxymethoxy)quinoline-2-carboxylic acid, ZINC ION, ... (4 entities in total)
• Functional Keywords: protein-foldamer complex, protein foldamer interactions, modified inhibitor, anchored foldamer, hcaii dimerisation, quinoline oligoamide foldamer, benzene sulfonamide modified inhibitor, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00918
• Total number of polymer chains: 2
• Total formula weight: 62103.19

Authors

Buratto, J.,Granier, T.,Langlois D'estaintot, B.,Huc, I.,Gallois, B. (deposition date: 2013-07-15, release date: 2013-10-23, Last modification date: 2024-03-13)

Primary citation

Buratto, J.,Colombo, C.,Stupfel, M.,Dawson, S.J.,Dolain, C.,Langlois d'Estaintot, B.,Fischer, L.,Granier, T.,Laguerre, M.,Gallois, B.,Huc, I.
Structure of a complex formed by a protein and a helical aromatic oligoamide foldamer at 2.1 angstrom resolution.
Angew.Chem.Int.Ed.Engl., 53:883-887, 2014

PubMed Abstract: In the search of molecules that could recognize sizeable areas of protein surfaces, a series of ten helical aromatic oligoamide foldamers was synthesized on solid phase. The foldamers comprise three to five monomers carrying various proteinogenic side chains, and exist as racemic mixtures of interconverting right-handed and left-handed helices. Functionalization of the foldamers by a nanomolar ligand of human carbonic anhydrase II (HCA) ensured that they would be held in close proximity to the protein surface. Foldamer-protein interactions were screened by circular dichroism (CD). One foldamer displayed intense CD bands indicating that a preferred helix handedness is induced upon interacting with the protein surface. The crystal structure of the complex between this foldamer and HCA could be resolved at 2.1 Å resolution and revealed a number of unanticipated protein-foldamer, foldamer-foldamer, and protein-protein interactions.

PubMed: 24288253
DOI: 10.1002/anie.201309160

Experimental method

X-RAY DIFFRACTION (2.15 Å)