3GW5

Crystal structure of human renin complexed with a novel inhibitor

Summary for 3GW5

• Entry DOI: 10.2210/pdb3gw5/pdb
• Descriptor: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, (3R)-3-[(1S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl]-N-{(1S)-2-cyclohexyl-1-[(methylamino)methyl]ethyl}piperidine-1-carboxamide, ... (7 entities in total)
• Functional Keywords: renin, aspartate protease, hypertension, renin expression, renin inhibitor, aspartyl protease, cleavage on pair of basic residues, disease mutation, disulfide bond, glycoprotein, hydrolase, membrane, protease, secreted, zymogen, 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: 76036.99

Authors

Wu, Z.,McKeever, B.M. (deposition date: 2009-03-31, release date: 2009-06-23, Last modification date: 2024-11-20)

Primary citation

Tice, C.M.,Xu, Z.,Yuan, J.,Simpson, R.D.,Cacatian, S.T.,Flaherty, P.T.,Zhao, W.,Guo, J.,Ishchenko, A.,Singh, S.B.,Wu, Z.,Scott, B.B.,Bukhtiyarov, Y.,Berbaum, J.,Mason, J.,Panemangalore, R.,Cappiello, M.G.,Muller, D.,Harrison, R.K.,McGeehan, G.M.,Dillard, L.W.,Baldwin, J.J.,Claremon, D.A.
Design and optimization of renin inhibitors: Orally bioavailable alkyl amines.
Bioorg.Med.Chem.Lett., 19:3541-3545, 2009

PubMed Abstract: Structure-based drug design led to the identification of a novel class of potent, low MW alkylamine renin inhibitors. Oral administration of lead compound 21l, with MW of 508 and IC(50) of 0.47nM, caused a sustained reduction in mean arterial blood pressure in a double transgenic rat model of hypertension.

PubMed: 19457666
DOI: 10.1016/j.bmcl.2009.04.140

Experimental method

X-RAY DIFFRACTION (2 Å)