BioDesign 2020; 8(3): 55-59
Published online September 30, 2020
© Korean Society for Structural Biology
Mi Rae Kim, Myeongbin Kim and Seong Eon Ryu*
Department of Bioengineering, College of Engineering, Hanyang University, Seoul 04763, Republic of Korea
Correspondence to: firstname.lastname@example.org
Protein tyrosine phosphatases (PTPs), along with protein kinases, mediate phosphorylation signaling in cells and are involved in cancers, diabetes, neural disorders, and immunological diseases. PTP sigma (PTPσ) is a receptor-type PTP with a C-terminal cytoplasmic region being responsible for its enzymatic activity. The inhibitors of the PTPσ catalytic activity promote neural cell growth and hematopoietic stem cell proliferation. In this study, we performed chemical library screening to identify a novel allosteric inhibitor PTPσ and characterized the inhibitor-enzyme interaction. Based on the analyses, we found a novel allosteric inhibitor that binds to a pocket between the two catalytic domains of the cytoplasmic region of PTPσ. Site directed mutagenesis studies identified residues involved in the inhibitor binding and enzyme kinetics experiments proved the allosteric mode of inhibition. The allosteric regulation site in the domain interface could be exploited to develop specific inhibitors for disease therapeutics.