spacer
spacer

PDBsum entry 1smr

Go to PDB code: 
protein ligands links
Hydrolase/hydrolase inhibitor PDB id
1smr
Jmol
Contents
Protein chains
331 a.a. *
Ligands
PIV-HIS-PRO-PHE-
HIS-LPL-TYR-TYR-
SER
×4
Waters ×156
* Residue conservation analysis
PDB id:
1smr
Name: Hydrolase/hydrolase inhibitor
Title: The 3-d structure of mouse submaxillary renin complexed with decapeptide inhibitor ch-66 based on the 4-16 fragment of r angiotensinogen
Structure: Renin. Chain: a, c, e, g. Engineered: yes. Inhibitor ch-66. Chain: b, d, f, h. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: cdna.
Biol. unit: Tetramer (from PQS)
Resolution:
2.00Å     R-factor:   0.180    
Authors: C.G.Dealwis,T.L.Blundell
Key ref: C.G.Dealwis et al. (1994). X-ray analysis at 2.0 A resolution of mouse submaxillary renin complexed with a decapeptide inhibitor CH-66, based on the 4-16 fragment of rat angiotensinogen. J Mol Biol, 236, 342-360. PubMed id: 8107115
Date:
11-Mar-92     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00796  (RENI2_MOUSE) -  Renin-2
Seq:
Struc:
401 a.a.
331 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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 Mol Biol 236:342-360 (1994)
PubMed id: 8107115  
 
 
X-ray analysis at 2.0 A resolution of mouse submaxillary renin complexed with a decapeptide inhibitor CH-66, based on the 4-16 fragment of rat angiotensinogen.
C.G.Dealwis, C.Frazao, M.Badasso, J.B.Cooper, I.J.Tickle, H.Driessen, T.L.Blundell, K.Murakami, H.Miyazaki, J.Sueiras-Diaz.
 
  ABSTRACT  
 
The structure of mouse submaxillary renin complexed with a decapeptide inhibitor, CH-66 (Piv-His-Pro-Phe-His-Leu-OH-Leu-Tyr-Tyr-Ser-NH2), where Piv denotes a pivaloyl blocking group, and -OH- denotes a hydroxyethylene (-(S)CHOH-CH2-) transition state isostere as a scissile bond surrogate, has been refined to an agreement factor of 0.18 at 2.0 A resolution. The positions of 10,038 protein atoms and 364 inhibitor atoms (4 independent protein inhibitor complexes), as well as of 613 solvent atoms, have been determined with an estimated root-mean-square (r.m.s.) error of 0.21 A. The r.m.s. deviation from ideality for bond distances is 0.026 A, and for angle distances is 0.0543 A. We have compared the three-dimensional structure of mouse renin with other aspartic proteinases, using rigid-body analysis with respect to shifts involving the domain comprising residues 190 to 302. In terms of the relative orientation of domains, mouse submaxillary renin is closest to human renin with only a 1.7 degrees difference in domain orientation. Porcine pepsin (the molecular replacement model) differs structurally from mouse renin by a 6.9 degrees domain rotation, whereas endothiapepsin, a fungal aspartic proteinase, differs by 18.8 degrees. The triple proline loop (residues 292 to 294), which is structurally opposite the active-site "flap" (residues 72 to 83), gives renin a superficial resemblance to the fold of the retroviral proteinases. The inhibitor is bound in an extended conformation along the active-site cleft, and the hydroxyethylene moiety forms hydrogen bonds with both catalytic aspartate carboxylates. The complex is stabilized by hydrogen bonds between the main chain of the inhibitor and the enzyme. All side-chains of the inhibitor are in van der Waals contact with groups in the enzyme and define ten specificity sub-sites. This study shows how renin has compact sub-sites due to the positioning of secondary structure elements, to complementary substitutions and to the residue composition of its loops close to the active site, leading to extreme specificity towards its prohormone substrate, angiotensinogen. We have analysed the micro-environment of each of the buried charged groups in order to predict their ionization states.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20927107 A.Zhou, R.W.Carrell, M.P.Murphy, Z.Wei, Y.Yan, P.L.Stanley, P.E.Stein, F.Broughton Pipkin, and R.J.Read (2010).
A redox switch in angiotensinogen modulates angiotensin release.
  Nature, 468, 108-111.
PDB codes: 2wxw 2wxx 2wxy 2wxz 2wy0 2wy1 2x0b
20015380 L.V.Mello, H.O'Meara, D.J.Rigden, and S.Paterson (2009).
Identification of novel aspartic proteases from Strongyloides ratti and characterisation of their evolutionary relationships, stage-specific expression and molecular structure.
  BMC Genomics, 10, 611.  
17485830 H.Iwata, T.Nakagawa, K.Nishiuchi, T.Hiratsuka, R.Satou, Y.Yoshioka, Y.Fukui, F.Suzuki, and Y.Nakamura (2007).
Ser84 of human renin contributes to the biphasic pH dependence of the renin-angiotensinogen reaction.
  Biosci Biotechnol Biochem, 71, 1279-1285.  
16537480 H.Xu, C.Faber, T.Uchiki, J.Racca, and C.Dealwis (2006).
Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly.
  Proc Natl Acad Sci U S A, 103, 4028-4033.
PDB code: 2eud
15039581 M.O.Badasso, V.Dhanaraj, S.P.Wood, J.B.Cooper, and T.L.Blundell (2004).
Crystallization and X-ray analysis of the Y75N mutant of Mucor pusillus pepsin complexed with inhibitor.
  Acta Crystallogr D Biol Crystallogr, 60, 770-772.  
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.  
11418762 S.W.Cho, N.Kim, M.U.Choi, and W.Shin (2001).
Structure of aspergillopepsin I from Aspergillus phoenicis: variations of the S1'-S2 subsite in aspartic proteinases.
  Acta Crystallogr D Biol Crystallogr, 57, 948-956.
PDB code: 1ibq
  11106168 C.A.Galea, B.P.Dalrymple, R.Kuypers, and R.Blakeley (2000).
Modification of the substrate specificity of porcine pepsin for the enzymatic production of bovine hide gelatin.
  Protein Sci, 9, 1947-1959.  
11021803 L.Hong, G.Koelsch, X.Lin, S.Wu, S.Terzyan, A.K.Ghosh, X.C.Zhang, and J.Tang (2000).
Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.
  Science, 290, 150-153.
PDB code: 1fkn
10488111 C.Frazão, I.Bento, J.Costa, C.M.Soares, P.Veríssimo, C.Faro, E.Pires, J.Cooper, and M.A.Carrondo (1999).
Crystal structure of cardosin A, a glycosylated and Arg-Gly-Asp-containing aspartic proteinase from the flowers of Cynara cardunculus L.
  J Biol Chem, 274, 27694-27701.
PDB code: 1b5f
  9514263 B.M.Beyer, and B.M.Dunn (1998).
Prime region subsite specificity characterization of human cathepsin D: the dominant role of position 128.
  Protein Sci, 7, 88-95.  
9485427 V.Olsen, K.Guruprasad, N.X.Cawley, H.C.Chen, T.L.Blundell, and Y.P.Loh (1998).
Cleavage efficiency of the novel aspartic protease yapsin 1 (Yap3p) enhanced for substrates with arginine residues flanking the P1 site: correlation with electronegative active-site pockets predicted by molecular modeling.
  Biochemistry, 37, 2768-2777.
PDB code: 1yps
9228062 T.Shintani, K.Nomura, and E.Ichishima (1997).
Engineering of porcine pepsin. Alteration of S1 substrate specificity of pepsin to those of fungal aspartic proteinases by site-directed mutagenesis.
  J Biol Chem, 272, 18855-18861.  
  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
7567964 C.Rao-Naik, K.Guruprasad, B.Batley, S.Rapundalo, J.Hill, T.Blundell, J.Kay, and B.M.Dunn (1995).
Exploring the binding preferences/specificity in the active site of human cathepsin E.
  Proteins, 22, 168-181.  
7540055 G.Siligardi, and A.F.Drake (1995).
The importance of extended conformations and, in particular, the PII conformation for the molecular recognition of peptides.
  Biopolymers, 37, 281-292.  
  7703859 D.Bailey, and J.B.Cooper (1994).
A structural comparison of 21 inhibitor complexes of the aspartic proteinase from Endothia parasitica.
  Protein Sci, 3, 2129-2143.
PDB codes: 1epl 1epm 1epn 1epr
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.  
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.