@article {85420,
	title = {Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP-9 and MMP-14},
	journal = {FEBS Lett},
	volume = {592},
	number = {7},
	year = {2018},
	note = {Shirian, JasonArkadash, ValeriaCohen, ItaySapir, TamilaRadisky, Evette SPapo, NivShifman, Julia MengR01 CA154387/CA/NCI NIH HHS/R21 CA205471/CA/NCI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tEnglandFEBS Lett. 2018 Apr;592(7):1122-1134. doi: 10.1002/1873-3468.13016. Epub 2018 Mar 12.},
	month = {Apr},
	pages = {1122-1134},
	edition = {2018/02/24},
	abstract = {MMP-14 and MMP-9 are two well-established cancer targets for which no specific clinically relevant inhibitor is available. Using a powerful combination of computational design and yeast surface display technology, we engineered such an inhibitor starting from a nonspecific MMP inhibitor, N-TIMP2. The engineered purified N-TIMP2 variants showed enhanced specificity toward MMP-14 and MMP-9 relative to a panel of off-target MMPs. MMP-specific N-TIMP2 sequence signatures were obtained that could be understood from the structural perspective of MMP/N-TIMP2 interactions. Our MMP-9 inhibitor exhibited 1000-fold preference for MMP-9 vs. MMP-14, which is likely to translate into significant differences under physiological conditions. Our results provide new insights regarding evolution of promiscuous proteins and optimization strategies for design of inhibitors with single-target specificities.},
	keywords = {*binding specificity, *matrix metalloproteinase inhibitors, *protein engineering, *protein-protein interactions, Humans, Matrix Metalloproteinase 14/chemical synthesis/*chemistry, Matrix Metalloproteinase 9/*chemistry, Matrix Metalloproteinase Inhibitors/*chemistry, Protein Binding, Tissue Inhibitor of Metalloproteinase-2/*chemistry},
	isbn = {1873-3468 (Electronic)0014-5793 (Linking)},
	author = {Shirian, J. and Arkadash, V. and Cohen, I. and Sapir, T. and Radisky, E. S. and Papo, N. and Shifman, J. M.}
}
