5VPM

Crystal Structure of Human Renin in Complex with a biphenylpipderidinylcarbinol

Summary for 5VPM

• Entry DOI: 10.2210/pdb5vpm/pdb
• Descriptor: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose, methyl [(4S)-4-(3'-ethyl-6-fluoro[1,1'-biphenyl]-2-yl)-4-hydroxy-4-{(3R)-1-[(piperidin-4-yl)acetyl]piperidin-3-yl}butyl]carbamate, ... (5 entities in total)
• Functional Keywords: renin inhibitor, biphenyl, hypertension, cyp 3a4, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P00797
• Total number of polymer chains: 2
• Total formula weight: 75621.15

Authors

Concha, N.,Zhao, B. (deposition date: 2017-05-05, release date: 2017-10-18, Last modification date: 2024-10-23)

Primary citation

Lawhorn, B.G.,Tran, T.,Hong, V.S.,Morgan, L.A.,Le, B.T.,Harpel, M.R.,Jolivette, L.,Diaz, E.,Schwartz, B.,Gross, J.W.,Tomaszek, T.,Semus, S.,Concha, N.,Smallwood, A.,Holt, D.A.,Kallander, L.S.
Discovery of renin inhibitors containing a simple aspartate binding moiety that imparts reduced P450 inhibition.
Bioorg. Med. Chem. Lett., 27:4838-4843, 2017

PubMed Abstract: Discovery of potent renin inhibitors which contain a simplified alkylamino Asp-binding group and exhibit improved selectivity for renin over Cyp3A4 is described. Structure-function results in this series are rationalized based on analysis of selected compounds bound to renin, and the contribution of each molecular feature leading to the reduced P450 inhibition is quantified.

PubMed: 28985999
DOI: 10.1016/j.bmcl.2017.09.046

Experimental method

X-RAY DIFFRACTION (2.9 Å)