PDBsum entry 2g22

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protein ligands links
Hydrolase PDB id
Protein chain
333 a.a. *
NAG ×2
6IG ×2
Waters ×87
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Ketopiperazine-based renin inhibitors: optimization of the "
Structure: Renin. Chain: a, b. Synonym: angiotensinogenase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ren. Expressed in: escherichia coli. Expression_system_taxid: 562
2.50Å     R-factor:   0.220     R-free:   0.256
Authors: D.D.Holsworth,M.Jalaiea,E.Zhanga,P.Mcconnella
Key ref: D.D.Holsworth et al. (2006). Ketopiperazine-based renin inhibitors: optimization of the "C" ring. Bioorg Med Chem Lett, 16, 2500-2504. PubMed id: 16480874 DOI: 10.1016/j.bmcl.2006.01.084
15-Feb-06     Release date:   13-Jun-06    
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Protein chains
Pfam   ArchSchema ?
P00797  (RENI_HUMAN) -  Renin
406 a.a.
333 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Renin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cleaves Leu-|- bond in angiotensinogen to generate angiotensin I.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     aspartic-type endopeptidase activity     1 term  


DOI no: 10.1016/j.bmcl.2006.01.084 Bioorg Med Chem Lett 16:2500-2504 (2006)
PubMed id: 16480874  
Ketopiperazine-based renin inhibitors: optimization of the "C" ring.
D.D.Holsworth, C.Cai, X.M.Cheng, W.L.Cody, D.M.Downing, N.Erasga, C.Lee, N.A.Powell, J.J.Edmunds, M.Stier, M.Jalaie, E.Zhang, P.McConnell, M.J.Ryan, J.Bryant, T.Li, A.Kasani, E.Hall, R.Subedi, M.Rahim, S.Maiti.
A systematic investigation of the S3 sub-pocket activity requirements was conducted. It was observed that linear and sterically small side chain substituents are preferred in the S3 sub-pocket for optimal renin inhibition. Polar groups in the S3-sub-pocket were not well tolerated and caused a reduction in renin inhibitory activity. Further, compounds with clog P's < or = 3 demonstrated a dramatic reduction in CYP3A4 inhibitory activity.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21376648 A.H.Al-Nadaf, and M.O.Taha (2011).
Discovery of new renin inhibitory leads via sequential pharmacophore modeling, QSAR analysis, in silico screening and in vitro evaluation.
  J Mol Graph Model, 29, 843-864.  
21429746 R.Aspiotis, A.Chen, E.Cauchon, D.Dubé, J.P.Falgueyret, S.Gagné, M.Gallant, E.L.Grimm, R.Houle, H.Juteau, P.Lacombe, S.Laliberté, J.F.Lévesque, D.MacDonald, D.McKay, M.D.Percival, P.Roy, S.M.Soisson, and T.Wu (2011).
The discovery and synthesis of potent zwitterionic inhibitors of renin.
  Bioorg Med Chem Lett, 21, 2430-2436.  
21497958 S.Thangapandian, S.John, S.Sakkiah, and K.W.Lee (2011).
Potential virtual lead identification in the discovery of renin inhibitors: application of ligand and structure-based pharmacophore modeling approaches.
  Eur J Med Chem, 46, 2469-2476.  
17680687 M.Brylinski, and J.Skolnick (2008).
What is the relationship between the global structures of apo and holo proteins?
  Proteins, 70, 363-377.  
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