Crystal Structure of Human E-Cadherin-EC1EC2 in Complex with a Peptidomimetic Competitive Inhibitor of Cadherin Homophilic Interaction.
Cadherins are transmembrane cell adhesion proteins whose aberrant expression often correlates with cancer development and proliferation. We report the crystal structure of an E-cadherin extracellular fragment in complex with a peptidomimetic compound that was previously shown to partially inhibit cadherin homophilic adhesion. The structure reveals an unexpected binding mode and allows the identification of a druggable cadherin interface, thus paving the way to a future structure-guided design of cell adhesion inhibitors against cadherin-expressing solid tumors.
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia , Via G. Pascoli 70/3, 20133 Milano, Italy.|Dipartimento di Chimica, Materiali and Ingegneria Chimica "Giulio Natta", Politecnico di Milano , Via L. Mancinelli 7, 20131 Milano, Italy.
Valentina
V
Nardone
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia , Via G. Pascoli 70/3, 20133 Milano, Italy.
Anna Paola
AP
Lucarelli
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia , Via G. Pascoli 70/3, 20133 Milano, Italy.|Dipartimento di Chimica, Materiali and Ingegneria Chimica "Giulio Natta", Politecnico di Milano , Via L. Mancinelli 7, 20131 Milano, Italy.
Andrea
A
Dalle Vedove
Dipartimento di Scienza e Alta Tecnologia, Università degli Studi dell'Insubria , Via Valleggio 11, 22100 Como, Italy.
Roberto
R
Fanelli
Dipartimento di Oncologia Sperimentale e Medicina Molecolare, Fondazione IRCCS Istituto Nazionale dei Tumori , Via G. Amadeo 42, 20133 Milano, Italy.
Antonella
A
Tomassetti
Dipartimento di Chimica, Università degli Studi di Milano , Via C. Golgi 19, 20133 Milano, Italy.
Laura
L
Belvisi
Dipartimento di Chimica, Università degli Studi di Milano , Via C. Golgi 19, 20133 Milano, Italy.
Monica
M
Civera
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia , Via G. Pascoli 70/3, 20133 Milano, Italy.
Emilio
E
Parisini
D015703:Antigens, CD; D001667:Binding, Competitive / Q000187:drug effects; D015820:Cadherins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D057786:Peptidomimetics / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D057786:Peptidomimetics