2V12

Crystal Structure of Renin with Inhibitor 8

Summary for 2V12

• Entry DOI: 10.2210/pdb2v12/pdb
• Related: 1BBS 1BIL 1BIM 1HRN 1PR7 1PR8 1RNE 1UHQ 2BKS 2BKT 2G20 2REN 2V0Z 2V10 2V11 2V13 2V16
• Descriptor: RENIN, N-[(2S,4S,5S,7R)-4-AMINO-8-(BUTYLAMINO)-5-HYDROXY-7-METHYL-2-(1-METHYLETHYL)-8-OXOOCTYL]-2-(3-METHOXYPROPOXY)BENZAMIDE (2 entities in total)
• Functional Keywords: glycoprotein, inhibitor-complex, aspartyl protease, zymogen, protease, hydrolase, polymorphism, alternative splicing, hydrolase(acid proteinase), cleavage on pair of basic residues
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 75521.37

Authors

Rahuel, J.,Rasetti, V.,Maibaum, J.,Rueger, H.,Goschke, R.,Cohen, N.C.,Stutz, S.,Cumin, F.,Fuhrer, W.,Wood, J.M.,Grutter, M.G. (deposition date: 2007-05-21, release date: 2007-07-03, Last modification date: 2024-11-13)

Primary citation

Rahuel, J.,Rasetti, V.,Maibaum, J.,Rueger, H.,Goschke, R.,Cohen, N.C.,Stutz, S.,Cumin, F.,Fuhrer, W.,Wood, J.M.,Grutter, M.G.
Structure-Based Drug Design: The Discovery of Novel Nonpeptide Orally Active Inhibitors of Human Renin
Chem.Biol., 7:493-, 2000

PubMed Abstract: The aspartic proteinase renin plays an important physiological role in the regulation of blood pressure. It catalyses the first step in the conversion of angiotensinogen to the hormone angiotensin II. In the past, potent peptide inhibitors of renin have been developed, but none of these compounds has made it to the end of clinical trials. Our primary aim was to develop novel nonpeptide inhibitors. Based on the available structural information concerning renin-substrate interactions, we synthesized inhibitors in which the peptide portion was replaced by lipophilic moieties that interact with the large hydrophobic S1/S3-binding pocket in renin.

PubMed: 10903938
DOI: 10.1016/S1074-5521(00)00134-4

Experimental method

X-RAY DIFFRACTION (3.2 Å)