spacer
spacer

PDBsum entry 2g1r

Go to PDB code: 
protein ligands links
Hydrolase PDB id
2g1r
Jmol
Contents
Protein chain
333 a.a. *
Ligands
NAG ×2
3IG ×2
Waters ×370
* Residue conservation analysis
PDB id:
2g1r
Name: Hydrolase
Title: Ketopiperazine-based renin inhibitors: optimization of the c
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
Resolution:
2.42Å     R-factor:   0.197     R-free:   0.240
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
Date:
14-Feb-06     Release date:   13-Jun-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00797  (RENI_HUMAN) -  Renin
Seq:
Struc:
406 a.a.
333 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.23.15  - 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.
 
  ABSTRACT  
 
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.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.