PDBsum entry 1bbs

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Aspartic proteinase PDB id
Protein chain
331 a.a. *
* Residue conservation analysis
PDB id:
Name: Aspartic proteinase
Title: X-ray analyses of peptide inhibitor complexes define the structural basis of specificity for human and mouse renins
Structure: Renin. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
2.80Å     R-factor:   0.196    
Authors: V.Dhanaraj,T.L.Blundell
Key ref: V.Dhanaraj et al. (1992). X-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins. Nature, 357, 466-472. PubMed id: 1608447 DOI: 10.1038/357466a0
21-May-92     Release date:   31-Jan-94    
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Protein chains
Pfam   ArchSchema ?
P00797  (RENI_HUMAN) -  Renin
406 a.a.
331 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     aspartic-type endopeptidase activity     1 term  


DOI no: 10.1038/357466a0 Nature 357:466-472 (1992)
PubMed id: 1608447  
X-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins.
V.Dhanaraj, C.G.Dealwis, C.Frazao, M.Badasso, B.L.Sibanda, I.J.Tickle, J.B.Cooper, H.P.Driessen, M.Newman, C.Aguilar.
X-ray analyses have defined the three-dimensional structures of crystals of mouse and human renins complexed with peptide inhibitors at resolutions of 1.9 and 2.8 A, respectively. The exquisite specificity of renin arises partly from ordered loop regions at the periphery of the binding cleft. Although the pattern of main-chain hydrogen bonding in other aspartic proteinase inhibitor complexes is conserved in renins, differences in the positions of secondary structure elements (particularly helices) also lead to improved specificity in renins for angiotensinogen substrates.

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.  
18175911 H.Iwata, T.Nakagawa, Y.Yoshioka, K.Kagei, K.Imada, C.Nakane, H.Fujita, F.Suzuki, and Y.Nakamura (2008).
The coexistence of Ser84 in renin and His13 in angiotensinogen brings a pH profile of two separate peaks to the reaction of human renin and sheep angiotensinogen.
  Biosci Biotechnol Biochem, 72, 179-185.  
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.  
17510964 C.Borelli, E.Ruge, M.Schaller, M.Monod, H.C.Korting, R.Huber, and K.Maskos (2007).
The crystal structure of the secreted aspartic proteinase 3 from Candida albicans and its complex with pepstatin A.
  Proteins, 68, 738-748.
PDB codes: 2h6s 2h6t
17447722 C.L.Parr, R.A.Keates, B.C.Bryksa, M.Ogawa, and R.Y.Yada (2007).
The structure and function of Saccharomyces cerevisiae proteinase A.
  Yeast, 24, 467-480.  
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.  
17700383 R.Sepehrdad, W.H.Frishman, C.T.Stier, and D.A.Sica (2007).
Direct inhibition of renin as a cardiovascular pharmacotherapy: focus on aliskiren.
  Cardiol Rev, 15, 242-256.  
17261087 T.Nakagawa, J.Akaki, R.Satou, M.Takaya, H.Iwata, A.Katsurada, K.Nishiuchi, Y.Ohmura, F.Suzuki, and Y.Nakamura (2007).
The His-Pro-Phe motif of angiotensinogen is a crucial determinant of the substrate specificity of renin.
  Biol Chem, 388, 237-246.  
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.  
11400666 G.Klebe (2001).
[Molecular modeling in the battle against AIDS. Drugs design in the development of substrate-like HIV protease inhibitors]
  Pharm Unserer Zeit, 30, 194-201.  
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.  
11495896 R.I.Brinkworth, P.Prociv, A.Loukas, and P.J.Brindley (2001).
Hemoglobin-degrading, aspartic proteases of blood-feeding parasites: substrate specificity revealed by homology models.
  J Biol Chem, 276, 38844-38851.  
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
10666618 J.B.Cooper, and D.A.Myles (2000).
A preliminary neutron Laue diffraction study of the aspartic proteinase endothiapepsin.
  Acta Crystallogr D Biol Crystallogr, 56, 246-248.  
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
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
10368289 R.M.Castillo, K.Mizuguchi, V.Dhanaraj, A.Albert, T.L.Blundell, and A.G.Murzin (1999).
A six-stranded double-psi beta barrel is shared by several protein superfamilies.
  Structure, 7, 227-236.  
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.  
9532792 U.M.Nasir, K.Takahashi, T.Nagai, T.Nakagawa, F.Suzuki, and Y.Nakamura (1998).
Two peaks in pH dependence of renin-angiotensinogen reaction.
  Biosci Biotechnol Biochem, 62, 338-340.  
9972250 Y.Inui, T.Orihashi, E.Okada, T.Nakagawa, A.Ebihara, F.Suzuki, and Y.Nakamura (1998).
Effects of substitution of Val for Leu11 of ovine angiotensinogen on renin activity.
  Biosci Biotechnol Biochem, 62, 2267-2269.  
  9377485 D.Arnold, W.Keilholz, H.Schild, T.Dumrese, S.Stevanović, and H.G.Rammensee (1997).
Evolutionary conserved cathepsin E substrate specificity as defined by N-terminal and C-terminal sequencing of peptide pools.
  Biol Chem, 378, 883-891.  
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.  
7880965 A.B.Smith, R.Akaishi, D.R.Jones, T.P.Keenan, M.C.Guzman, R.C.Holcomb, P.A.Sprengeler, J.L.Wood, R.Hirschmann, and M.K.Holloway (1995).
Design and synthesis of nonpeptide peptidomimetic inhibitors of renin.
  Biopolymers, 37, 29-53.  
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.  
7575336 J.Peters (1995).
Molecular basis of human hypertension: the role of angiotensin.
  Baillieres Clin Endocrinol Metab, 9, 657-678.  
8747465 J.R.Tame, E.J.Dodson, G.Murshudov, C.F.Higgins, and A.J.Wilkinson (1995).
The crystal structures of the oligopeptide-binding protein OppA complexed with tripeptide and tetrapeptide ligands.
  Structure, 3, 1395-1406.
PDB codes: 1olc 2olb
  7576490 L.Pilote, G.McKercher, D.Thibeault, and D.Lamarre (1995).
Enzymatic characterization of purified recombinant human renin.
  Biochem Cell Biol, 73, 163-170.  
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
8591036 S.M.Cutfield, E.J.Dodson, B.F.Anderson, P.C.Moody, C.J.Marshall, P.A.Sullivan, and J.F.Cutfield (1995).
The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors.
  Structure, 3, 1261-1271.
PDB code: 1eag
  7833817 A.Sali, and J.P.Overington (1994).
Derivation of rules for comparative protein modeling from a database of protein structure alignments.
  Protein Sci, 3, 1582-1596.  
  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
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.  
  8143488 M.S.Johnson, N.Srinivasan, R.Sowdhamini, and T.L.Blundell (1994).
Knowledge-based protein modeling.
  Crit Rev Biochem Mol Biol, 29, 1.  
8035212 S.D.Rufino, and T.L.Blundell (1994).
Structure-based identification and clustering of protein families and superfamilies.
  J Comput Aided Mol Des, 8, 5.  
8047064 T.Hatae, E.Takimoto, K.Murakami, and A.Fukamizu (1994).
Comparative studies on species-specific reactivity between renin and angiotensinogen.
  Mol Cell Biochem, 131, 43-47.  
8393577 E.T.Baldwin, T.N.Bhat, S.Gulnik, M.V.Hosur, R.C.Sowder, R.E.Cachau, J.Collins, A.M.Silva, and J.W.Erickson (1993).
Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design.
  Proc Natl Acad Sci U S A, 90, 6796-6800.
PDB codes: 1lya 1lyb
  8467789 P.Metcalf, and M.Fusek (1993).
Two crystal structures for cathepsin D: the lysosomal targeting signal and active site.
  EMBO J, 12, 1293-1302.  
8259000 S.S.Abdel-Meguid (1993).
Inhibitors of aspartyl proteinases.
  Med Res Rev, 13, 731-778.  
  8302216 W.G.Dougherty, and B.L.Semler (1993).
Expression of virus-encoded proteinases: functional and structural similarities with cellular enzymes.
  Microbiol Rev, 57, 781-822.  
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.