Structural highlights
FunctionIPGC_SHIFL Assists the correct folding of nascent IpaB. Once it is bound to IpaB, it binds to IpaC and impedes their premature association that would lead to their degradation in the absence of IpcG. Publication Abstract from PubMedThe Shigella 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 Shigella 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. Crystallographic Fragment Screening on the Shigella Type III Secretion System Chaperone IpgC.,Gardonyi M, Hasewinkel C, Wallbaum J, Wollenhaupt J, Weiss MS, Klebe G, Reuter K, Heine A ACS Omega. 2023 Nov 20;8(48):46051-46065. doi: 10.1021/acsomega.3c07058. , eCollection 2023 Dec 5. PMID:38075755[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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