8QH6

Crystal structure of IpgC in complex with a follow-up compound based on J20

Summary for 8QH6

• Entry DOI: 10.2210/pdb8qh6/pdb
• Related: 6SCB
• Descriptor: Chaperone protein IpgC, 3-azanyl-6-chloranyl-isoindol-1-one, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: complex, 3-amino-6-chloro-1h-isoindol-1-one, chaperone
• Biological source: Shigella flexneri
• Total number of polymer chains: 2
• Total formula weight: 32921.09

Authors

Wallbaum, J.E.,Heine, A.,Reuter, K. (deposition date: 2023-09-06, release date: 2023-12-27)

Primary citation

Gardonyi, M.,Hasewinkel, C.,Wallbaum, J.,Wollenhaupt, J.,Weiss, M.S.,Klebe, G.,Reuter, K.,Heine, A.
Crystallographic Fragment Screening on the Shigella Type III Secretion System Chaperone IpgC.
Acs Omega, 8:46051-46065, 2023

PubMed Abstract: The pathogenicity factor IpgC belongs to the class II of type III secretion system chaperones, whose members are characterized by a tetratricopeptide repeat (TPR) domain consisting of three and a half TPR motifs. Since IpgC is essential for virulence, we determined a high-resolution crystal structure of this chaperone to facilitate its use as a target for the structure-based design of anti-shigellosis compounds. The crystal structure revealed two possible homodimer assemblies, which strongly differ from the homodimer architectures so far known for IpgC and orthologues thereof. Through crystallographic fragment screening, we identified 10 small molecules that bind to IpgC and, therefore, are available for expansion to generate larger, more potent binders. A follow-up compound, based on one of our fragment hits, binds to a strictly conserved site, which overlaps with the binding site of the chaperone's substrates, IpaB and IpaC. Therefore, it constitutes a promising starting point for the design of functional IpgC inhibitors.

PubMed: 38075755
DOI: 10.1021/acsomega.3c07058

Experimental method

X-RAY DIFFRACTION (1.8 Å)