Many processes in a living cell are regulated through the specific interaction between proteins. Targeting the disruption of protein-protein complexes for therapeutic purposes is considered a very attractive, albeit difficult, approach. In our research, we take advantage of information on the protein's overall fold, primary and secondary structure at the interface and flexibility to identify putative binding sites and design and test molecules that interfere with or block protein-protein interaction. We focus on peptides, peptidomimetics, and small molecular weight compounds.
Reinhart EF, Litt NA, Katzenell S, Pellegrini M, Yamamoto A, Ragusa MJ. A highly conserved glutamic acid in ALFY inhibits membrane binding to aid in aggregate clearance. Traffic. 2021 Jan;22(1-2):23-37. doi: 10.1111/tra.12771. Epub 2020 Dec 1. PubMed PMID: 33225481; PubMed Central PMCID: PMC7902475.
Midgett CR, Swindell RA, Pellegrini M, Jon Kull F. A disulfide constrains the ToxR periplasmic domain structure, altering its interactions with ToxS and bile-salts. Sci Rep. 2020 Jun 2;10(1):9002. doi: 10.1038/s41598-020-66050-5. PubMed PMID: 32488093; PubMed Central PMCID: PMC7265457.
Barczewski AH, Ragusa MJ, Mierke DF, Pellegrini M. Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO. J Vis Exp. 2019 Dec 28;(154). doi: 10.3791/60339. PubMed PMID: 31929506; PubMed Central PMCID: PMC7359928.
Bauer KM, Dicovitsky R, Pellegrini M, Zhaxybayeva O, Ragusa MJ. The structure of a highly-conserved picocyanobacterial protein reveals a Tudor domain with an RNA-binding function. J Biol Chem. 2019 Sep 27;294(39):14333-14344. doi: 10.1074/jbc.RA119.007938. Epub 2019 Aug 7. PubMed PMID: 31391250; PubMed Central PMCID: PMC6768636.
NESS - North Eastern Structure Symposium 2014: Structural Biology of Inflammation
"Fishin' for Inhibitors of NEMO"