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PDBsum entry 2i4q

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
2i4q
Jmol
Contents
Protein chain
336 a.a. *
Ligands
UA4 ×2
Waters ×190
* Residue conservation analysis
PDB id:
2i4q
Name: Hydrolase
Title: Human renin/pf02342674 complex
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
Biol. unit: Hexamer (from PQS)
Resolution:
2.30Å     R-factor:   0.230     R-free:   0.261
Authors: D.D.Holsworth,M.Jalaie,E.Zhang,P.Mcconnell,I.Mochalkin, B.C.Finzel
Key ref: N.A.Powell et al. (2007). Rational design of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as small molecule renin inhibitors. Bioorg Med Chem, 15, 5912-5949. PubMed id: 17574423
Date:
22-Aug-06     Release date:   24-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00797  (RENI_HUMAN) -  Renin
Seq:
Struc:
406 a.a.
336 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  

 

 
Bioorg Med Chem 15:5912-5949 (2007)
PubMed id: 17574423  
 
 
Rational design of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as small molecule renin inhibitors.
N.A.Powell, F.L.Ciske, C.Cai, D.D.Holsworth, K.Mennen, C.A.Van Huis, M.Jalaie, J.Day, M.Mastronardi, P.McConnell, I.Mochalkin, E.Zhang, M.J.Ryan, J.Bryant, W.Collard, S.Ferreira, C.Gu, R.Collins, J.J.Edmunds.
 
  ABSTRACT  
 
We report the design and synthesis of a series of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as orally bioavailable small molecule inhibitors of renin. Compounds with a 2-methyl-2-aryl substitution pattern exhibit potent renin inhibition and good permeability, solubility, and metabolic stability. Oral bioavailability was found to be dependent on metabolic clearance and cellular permeability, and was optimized through modulation of the sidechain that binds in the S3(sp) subsite.
 

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.  
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