9Q1H

A7 minibinder in complex with Abp2D

Summary for 9Q1H

• Entry DOI: 10.2210/pdb9q1h/pdb
• Descriptor: Minibinder A7, Abp2D Receptor Binding Domain (3 entities in total)
• Functional Keywords: inhibitor, complex, de novo protein, adhesin, protein binding
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 26137.27

Authors

Lopatto, E.D.B.,Tamadonfar, K.O.,Hultgren, S.J. (deposition date: 2025-08-13, release date: 2025-09-17)

Primary citation

Chazin-Gray, A.M.,Thompson, T.R.,Lopatto, E.D.B.,Magala, P.,Erickson, P.W.,Hunt, A.C.,Manchenko, A.,Aprikian, P.,Tchesnokova, V.,Basova, I.,Sanick, D.A.,Tamadonfar, K.O.,Timm, M.R.,Pinkner, J.S.,Dodson, K.W.,Kang, A.,Joyce, E.,Bera, A.K.,Schmitz, A.J.,Ellebedy, A.H.,Hvorecny, K.L.,Cartwright, M.J.,Vernet, A.,Bardales, S.,White, D.,Klevit, R.E.,Sokurenko, E.V.,Hultgren, S.J.,Baker, D.
De Novo Design of Miniprotein Inhibitors of Bacterial Adhesins.
Biorxiv, 2025

PubMed Abstract: The rise of multidrug-resistant bacterial infections necessitates the discovery of novel antimicrobial strategies. Here, we show that protein design provides a generalizable means of generating new antimicrobials by neutralizing the function of bacterial adhesins, which are virulence factors critical in host-pathogen interactions. We designed high-affinity miniprotein binders to FimH and Abp1D/Abp2D chaperone usher pili adhesins from uropathogenic and , respectively, which are implicated in mediating both uncomplicated and catheter-associated urinary tract infections (UTI) responsible for significant morbidity and mortality worldwide. The designed antagonists have high specificity and stability, disrupt bacterial recognition of host receptors, block biofilm formation, and are effective in treating and preventing uncomplicated and catheter-associated UTIs . Targeting virulence factors outside the cell membrane with protein design provides a rapid route to next-generation therapeutics that can disrupt pathogenesis and thus are capable of treating and preventing disease in an antibiotic-sparing manner.

PubMed: 40894640
DOI: 10.1101/2025.08.18.670751

Experimental method

X-RAY DIFFRACTION (1.35 Å)