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PDBsum entry 1rne

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Hydrolase(acid proteinase) PDB id
1rne
Jmol
Contents
Protein chain
330 a.a. *
Ligands
NGA
C60
Waters ×138
* Residue conservation analysis
PDB id:
1rne
Name: Hydrolase(acid proteinase)
Title: The crystal structure of recombinant glycosylated human renin alone and in complex with a transition state analog inhibitor
Structure: Renin. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: ovary
Biol. unit: Dimer (from PQS)
Resolution:
2.40Å     R-factor:   0.176    
Authors: M.G.Gruetter,J.Rahuel,J.P.Priestle
Key ref: J.Rahuel et al. (1991). The crystal structures of recombinant glycosylated human renin alone and in complex with a transition state analog inhibitor. J Struct Biol, 107, 227-236. PubMed id: 1807356
Date:
12-Dec-91     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00797  (RENI_HUMAN) -  Renin
Seq:
Struc:
406 a.a.
330 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  

 

 
J Struct Biol 107:227-236 (1991)
PubMed id: 1807356  
 
 
The crystal structures of recombinant glycosylated human renin alone and in complex with a transition state analog inhibitor.
J.Rahuel, J.P.Priestle, M.G.Grütter.
 
  ABSTRACT  
 
Recombinant human glycosylated renin has been crystallized in complex with CGP 38'560, a transition state analog inhibitor (IC50 = 2 x 10(-9) M), in a tetragonal crystal form. The structure has been determined to a resolution of 2.4 A and refined to a crystallographic Rfactor of 17.6%. It reveals the conformation of the inhibitor as well as its interactions with the enzyme active site. The active site is a deep cleft between the N- and the C-terminal domains to which the inhibitor binds in an extended conformation filling the S4 to S2' pockets. The structure of the complex is compared with that of the related uninhibited enzyme pepsin. Significant changes in the relative orientation of the N- and C-terminal domains are observed. In the inhibited renin structure the C-terminal loop segments forming the active site are closer to those from the N-terminal domain than in the related "open" pepsin structure. In addition, the structure of uninhibited glycosylated renin has been determined at 2.8 A resolution from a cubic crystal form with two renin molecules in the asymmetric unit. The two independent renin molecules show different conformations with respect to the relative orientation of their N- and C-terminal domains; one molecule is found in the "closed inhibited" conformation, the other in the "open uninhibited" conformation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21036942 A.Michaud, D.Bur, O.Gribouval, L.Muller, X.Iturrioz, M.Clemessy, J.M.Gasc, M.C.Gubler, and P.Corvol (2011).
Loss-of-function point mutations associated with renal tubular dysgenesis provide insights about renin function and cellular trafficking.
  Hum Mol Genet, 20, 301-311.  
19893565 A.H.Danser (2010).
The increase in renin during renin inhibition: does it result in harmful effects by the (pro)renin receptor?
  Hypertens Res, 33, 4.  
18764720 H.Siragy, J.Huang, and D.C.Lieb (2008).
The development of the direct renin inhibitor aliskiren: treating hypertension and beyond.
  Expert Opin Emerg Drugs, 13, 417-430.  
17703126 A.H.Danser (2007).
Novel drugs targeting hypertension: renin inhibitors.
  J Cardiovasc Pharmacol, 50, 105-111.  
15048822 J.M.Yang, and C.C.Chen (2004).
GEMDOCK: a generic evolutionary method for molecular docking.
  Proteins, 55, 288-304.  
12838268 S.J.Teague (2003).
Implications of protein flexibility for drug discovery.
  Nat Rev Drug Discov, 2, 527-541.  
11714911 N.S.Andreeva, and L.D.Rumsh (2001).
Analysis of crystal structures of aspartic proteinases: on the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes.
  Protein Sci, 10, 2439-2450.  
10074464 C.Oefner, A.Binggeli, V.Breu, D.Bur, J.P.Clozel, A.D'Arcy, A.Dorn, W.Fischli, F.Grüninger, R.Güller, G.Hirth, H.Märki, S.Mathews, M.M ller, R.G.Ridley, H.Stadler, E.Vieira, M.Wilhelm, F.Winkler, and W.Wostl (1999).
Renin inhibition by substituted piperidines: a novel paradigm for the inhibition of monomeric aspartic proteinases?
  Chem Biol, 6, 127-131.
PDB codes: 1pr7 1pr8
10427707 U.M.Nasir, F.Suzuki, T.Nagai, T.Nakagawa, and Y.Nakamura (1999).
Tyrosine-83 of human renin contributes to biphasic pH dependence of the renin-angiotensinogen reaction.
  Biosci Biotechnol Biochem, 63, 1143-1145.  
  8845753 C.Abad-Zapatero, R.Goldman, S.W.Muchmore, C.Hutchins, K.Stewart, J.Navaza, C.D.Payne, and T.L.Ray (1996).
Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents.
  Protein Sci, 5, 640-652.
PDB code: 1zap
  8976570 F.Grueninger-Leitch, A.D'Arcy, B.D'Arcy, and C.Chène (1996).
Deglycosylation of proteins for crystallization using recombinant fusion protein glycosidases.
  Protein Sci, 5, 2617-2622.  
8877698 H.J.Böhm (1996).
Towards the automatic design of synthetically accessible protein ligands: peptides, amides and peptidomimetics.
  J Comput Aided Mol Des, 10, 265-272.  
8706738 M.Malissard, L.Borsig, S.Di Marco, M.G.Grütter, U.Kragl, C.Wandrey, and E.G.Berger (1996).
Recombinant soluble beta-1,4-galactosyltransferases expressed in Saccharomyces cerevisiae. Purification, characterization and comparison with human enzyme.
  Eur J Biochem, 239, 340-348.  
9222997 J.Gante, M.Krug, G.Lauterbach, R.Weitzel, and W.Hiller (1995).
Synthesis and properties of the first all-aza analogue of a biologically active peptide.
  J Pept Sci, 1, 201-206.  
7493993 L.Tong, S.Pav, D.Lamarre, B.Simoneau, P.Lavallée, and G.Jung (1995).
Crystallographic studies on the binding modes of P2-P3 butanediamide renin inhibitors.
  J Biol Chem, 270, 29520-29524.
PDB codes: 1bil 1bim
7938177 J.M.Wood, F.Cumin, and J.Maibaum (1994).
Pharmacology of renin inhibitors and their application to the treatment of hypertension.
  Pharmacol Ther, 61, 325-344.  
7824526 S.Pav, K.Lubbe, F.Dô, D.Lamarre, C.Pargellis, and L.Tong (1994).
Microtube batch protein crystallization: applications to human immunodeficiency virus type 2 (HIV-2) protease and human renin.
  Proteins, 20, 98.  
8060670 H.J.Böhm (1993).
A novel computational tool for automated structure-based drug design.
  J Mol Recognit, 6, 131-137.  
8259000 S.S.Abdel-Meguid (1993).
Inhibitors of aspartyl proteinases.
  Med Res Rev, 13, 731-778.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.