Publication about this research Y Zhang M Ultsch N Skelton S Burdick M Beresini W Li M KongBeltran A Peterson J Quinn C Chiu Y Wu S Shia P Moran P Di Lello ID: 1009488
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1. A peptide that has successfully bound to PCSK9 is now able to block the low-density lipoprotein (LDL) receptor.Publication about this research: Y. Zhang, M. Ultsch, N. Skelton, S. Burdick, M. Beresini, W. Li, M. Kong-Beltran, A. Peterson, J. Quinn, C. Chiu, Y. Wu, S. Shia, P. Moran, P. Di Lello, C. Eigenbrot, and D. Kirchhofer, Nat. Struct. Mol. Biol. 24, 848 (2017). Work was performed at Lawrence Berkeley National Laboratory, ALS Beamline 5.0.2. Operation of the ALS is supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences program. Genentech Advances New Cholesterol-Lowering TreatmentsScientific AchievementUsing ALS crystallography capabilities, Genentech discovered a “cryptic” (hidden) binding site on the cholesterol-regulating protein PCSK9.Significance and ImpactThe discovery advances Genentech’s goal of developing a new type of small-molecule drug that effectively lowers cholesterol with less disruption, fewer side effects, and lower cost than current treatments.Research DetailsPCSK9 interferes with LDL (“bad”) cholesterol removal by binding to the LDL receptor protein.ALS data showed that PCSK9’s structure can dynamically change shape, revealing a vacated groove next to the LDL receptor binding site.Genentech engineered peptides that attach to the groove and encroach on the binding site, inhibiting LDL receptor binding.