PDBsum entry 1pip

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Hydrolase/hydrolase inhibitor PDB id
Protein chain
212 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of papain-succinyl-gln-val-val-ala-ala-p- nitroanilide complex at 1.7 angstroms resolution: noncovale mode of a common sequence of endogenous thiol protease inhi
Structure: Papain. Chain: a. Engineered: yes. Succinyl-gln-val-val-ala-ala-p-nitroanilide. Chain: b. Engineered: yes
Source: Carica papaya. Papaya. Organism_taxid: 3649. Synthetic: yes
Biol. unit: Dimer (from PQS)
1.70Å     R-factor:   0.196    
Authors: A.Yamamoto,K.Tomoo,M.Doi,H.Ohishi,M.Inoue,T.Ishida,D.Yamamot S.Tsuboi,H.Okamoto,Y.Okada
Key ref:
A.Yamamoto et al. (1992). Crystal structure of papain-succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide complex at 1.7-A resolution: noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors. Biochemistry, 31, 11305-11309. PubMed id: 1445868 DOI: 10.1021/bi00161a007
03-Oct-92     Release date:   31-Oct-93    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00784  (PAPA1_CARPA) -  Papain
345 a.a.
212 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Papain.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins with broad specificity for peptide bonds, with preference for a residue bearing a large hydrophobic sidechain at the P2 position. Does not accept Val at P1'.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     cysteine-type peptidase activity     1 term  


DOI no: 10.1021/bi00161a007 Biochemistry 31:11305-11309 (1992)
PubMed id: 1445868  
Crystal structure of papain-succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide complex at 1.7-A resolution: noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors.
A.Yamamoto, K.Tomoo, M.Doi, H.Ohishi, M.Inoue, T.Ishida, D.Yamamoto, S.Tsuboi, H.Okamoto, Y.Okada.
Succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide corresponding to a common sequence of endogenous thiol protease inhibitors is a noncompetitive reversible inhibitor of papain. In order to elucidate the binding mode of the inhibitor at the atomic level, its complex with papain was crystallized at ca. pH 7.0 using the hanging drop method, and the crystal structure was analyzed at 1.7-A resolution. The crystal has space group P2(1)2(1)2(1), with a = 43.09, b = 102.32, c = 49.69 A, and Z = 4. A total of 47,215 observed reflections were collected on the imaging plates using the same single crystal, and 19,833 unique reflections with Fo > sigma (Fo) were used for structure determination and refinement. The papain structure was determined by use of the atomic coordinates of papain previously reported, and then refined by the X-PLOR program. The inhibitor molecule was located on a difference Fourier map and fitted into the electron density with the aid of computer graphics. The complex structure was finally refined to R = 19.6% including 118 solvent molecules. The X-ray analysis of the complex crystal shows that the inhibitor is located at the R-domain side, not in the center of the binding site created by the R- and L-domains of papain. Such a binding mode of the inhibitor explains well the biological behavior that the inhibitor exhibits against papain. Comparison with the structure of papain-stefin B complex indicates that the structure of the Gln-Val-Val-Ala-Gly sequence itself is not necessarily the essential requisite for inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Literature references that cite this PDB file's key reference

  PubMed id Reference
20410261 F.Xue, Y.Sun, L.Yan, C.Zhao, J.Chen, M.Bartlam, X.Li, Z.Lou, and Z.Rao (2010).
The crystal structure of porcine reproductive and respiratory syndrome virus nonstructural protein Nsp1beta reveals a novel metal-dependent nuclease.
  J Virol, 84, 6461-6471.
PDB code: 3mtv
19706710 Y.Sun, F.Xue, Y.Guo, M.Ma, N.Hao, X.C.Zhang, Z.Lou, X.Li, and Z.Rao (2009).
Crystal structure of porcine reproductive and respiratory syndrome virus leader protease Nsp1alpha.
  J Virol, 83, 10931-10940.
PDB code: 3ifu
15739204 J.Ko, L.F.Murga, P.André, H.Yang, M.J.Ondrechen, R.J.Williams, A.Agunwamba, and D.E.Budil (2005).
Statistical criteria for the identification of protein active sites using Theoretical Microscopic Titration Curves.
  Proteins, 59, 183-195.  
12833545 M.Sulpizi, A.Laio, J.VandeVondele, A.Cattaneo, U.Rothlisberger, and P.Carloni (2003).
Reaction mechanism of caspases: insights from QM/MM Car-Parrinello simulations.
  Proteins, 52, 212-224.  
10350606 C.Czaplewski, Z.Grzonka, M.Jaskólski, F.Kasprzykowski, M.Kozak, E.Politowska, and J.Ciarkowski (1999).
Binding modes of a new epoxysuccinyl-peptide inhibitor of cysteine proteases. Where and how do cysteine proteases express their selectivity?
  Biochim Biophys Acta, 1431, 290-305.  
10614065 K.D.Randell, T.P.Frandsen, B.Stoffer, M.A.Johnson, B.Svensson, and B.M.Pinto (1999).
Synthesis and glycosidase inhibitory activity of 5-thioglucopyranosylamines. Molecular modeling of complexes with glucoamylase.
  Carbohydr Res, 321, 143-156.  
10410800 M.E.McGrath (1999).
The lysosomal cysteine proteases.
  Annu Rev Biophys Biomol Struct, 28, 181-204.  
9857201 A.Guarné, J.Tormo, R.Kirchweger, D.Pfistermueller, I.Fita, and T.Skern (1998).
Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition.
  EMBO J, 17, 7469-7479.
PDB code: 1qol
  9524065 D.Turk, G.Guncar, M.Podobnik, and B.Turk (1998).
Revised definition of substrate binding sites of papain-like cysteine proteases.
  Biol Chem, 379, 137-147.  
9253409 L.Jin, B.A.Seaton, and J.F.Head (1997).
Crystal structure at 2.8 A resolution of anabolic ornithine transcarbamylase from Escherichia coli.
  Nat Struct Biol, 4, 622-625.
PDB code: 1akm
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