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PDBsum entry 1pe6
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Hydrolase (sulfhydryl proteinase) PDB id
1pe6

 

 

 

 

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Contents
Protein chain
212 a.a. *
Ligands
E6C
MOH ×14
Waters ×181
* Residue conservation analysis
PDB id:
1pe6
Name: Hydrolase (sulfhydryl proteinase)
Title: Refined x-ray structure of papain(dot)e-64-c complex at 2.1-angstroms resolution
Structure: Papain. Chain: a. Engineered: yes
Source: Carica papaya. Papaya. Organism_taxid: 3649
Resolution:
2.10Å     R-factor:   0.159    
Authors: D.Yamamoto,K.Matsumoto,H.Ohishi,T.Ishida,M.Inoue,K.Kitamura,H.Mizuno
Key ref: D.Yamamoto et al. (1991). Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution. J Biol Chem, 266, 14771-14777. PubMed id: 1860874
Date:
14-May-91     Release date:   15-Apr-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00784  (PAPA1_CARPA) -  Papain from Carica papaya
Seq:
Struc: 		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.3.4.22.2  - 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'.

 

 
J Biol Chem 266:14771-14777 (1991)
PubMed id: 1860874  
 
 
Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution.
D.Yamamoto, K.Matsumoto, H.Ohishi, T.Ishida, M.Inoue, K.Kitamura, H.Mizuno.
 
  ABSTRACT  
 
E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A resolution were used to determine the three-dimensional structure of this complex and refined it to R = 0.159. 0.159. In the complex structure, the configurational conversion from S to R took place on the epoxy carbon of E-64-c, implying that the nucleophilic attack of the Cys-25 thiol group occurs at the opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of E-64-c were strongly fixed to papain S subsites by specific interactions, including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of E-64-c formed an electrostatic interaction with the protonated His-159 imidazole ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this residue in the hydrolytic charge-relay system. No significant distortion caused by the binding of E-64-c was shown in the secondary structure of papain. It is important to note that inhibitor and substrate have opposite binding modes for the peptide groups. The possible relationship between the binding mode and inhibitory activity is discussed on the basis of the crystal structure of this complex.
 

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
19952439 T.Ishida (2009).
Structural studies of specific intermolecular interactions and self-aggregation of biomolecules and their application to drug design.
  Chem Pharm Bull (Tokyo), 57, 1309-1334.  
19430116 T.K.Nandi, H.R.Bairagya, B.P.Mukhopadhyay, K.Sekar, D.Sukul, and A.K.Bera (2009).
Conserved water-mediated H-bonding dynamics of catalytic Asn 175 in plant thiol protease.
  J Biosci, 34, 27-34.  
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
16020535 G.Nicastro, R.P.Menon, L.Masino, P.P.Knowles, N.Q.McDonald, and A.Pastore (2005).
The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition.
  Proc Natl Acad Sci U S A, 102, 10493-10498.
PDB code: 1yzb
14725770 Y.Zong, S.K.Mazmanian, O.Schneewind, and S.V.Narayana (2004).
The structure of sortase B, a cysteine transpeptidase that tethers surface protein to the Staphylococcus aureus cell wall.
  Structure, 12, 105-112.
PDB codes: 1qwz 1qx6 1qxa
12554931 D.Turk, and G.Guncar (2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
  Acta Crystallogr D Biol Crystallogr, 59, 203-213.  
14559965 J.Blanco, R.A.Moore, and R.E.Viola (2003).
Capture of an intermediate in the catalytic cycle of L-aspartate-beta-semialdehyde dehydrogenase.
  Proc Natl Acad Sci U S A, 100, 12613-12617.
PDB codes: 1nwc 1nwh 1nx6
12784208 S.Biswas, C.Chakrabarti, S.Kundu, M.V.Jagannadham, and J.K.Dattagupta (2003).
Proposed amino acid sequence and the 1.63 A X-ray crystal structure of a plant cysteine protease, ervatamin B: some insights into the structural basis of its stability and substrate specificity.
  Proteins, 51, 489-497.
PDB code: 1iwd
11440138 K.Isshiki, Y.Asai, S.Tanaka, M.Nishio, T.Uchida, T.Okuda, S.Komatsubara, and N.Sakurai (2001).
Aurantiamide acetate, a selective cathepsin inhibitor, produced by Aspergillus penicilloides.
  Biosci Biotechnol Biochem, 65, 1195-1197.  
11602025 S.Bhattacharya, S.Ghosh, S.Chakraborty, A.K.Bera, B.P.Mukhopadhayay, I.Dey, and A.Banerjee (2001).
Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : understanding the basis of differential inhibition and the role of water.
  BMC Struct Biol, 1, 4.  
10380357 K.Matsumoto, K.Mizoue, K.Kitamura, W.C.Tse, C.P.Huber, and T.Ishida (1999).
Structural basis of inhibition of cysteine proteases by E-64 and its derivatives.
  Biopolymers, 51, 99.  
10601364 L.Gough, O.Schulz, H.F.Sewell, and F.Shakib (1999).
The cysteine protease activity of the major dust mite allergen Der p 1 selectively enhances the immunoglobulin E antibody response.
  J Exp Med, 190, 1897-1902.  
10410800 M.E.McGrath (1999).
The lysosomal cysteine proteases.
  Annu Rev Biophys Biomol Struct, 28, 181-204.  
10470376 N.Katunuma, A.Matsui, T.Kakegawa, E.Murata, T.Asao, and Y.Ohba (1999).
Study of the functional share of lysosomal cathepsins by the development of specific inhibitors.
  Adv Enzyme Regul, 39, 247-260.  
10380356 T.Schirmeister (1999).
Inhibition of cysteine proteases by peptides containing aziridine-2,3-dicarboxylic acid building blocks.
  Biopolymers, 51, 87-97.  
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.  
9033588 B.Zhao, C.A.Janson, B.Y.Amegadzie, K.D'Alessio, C.Griffin, C.R.Hanning, C.Jones, J.Kurdyla, M.McQueney, X.Qiu, W.W.Smith, and S.S.Abdel-Meguid (1997).
Crystal structure of human osteoclast cathepsin K complex with E-64.
  Nat Struct Biol, 4, 109-111.
PDB code: 1atk
9033587 M.E.McGrath, J.L.Klaus, M.G.Barnes, and D.Brömme (1997).
Crystal structure of human cathepsin K complexed with a potent inhibitor.
  Nat Struct Biol, 4, 105-109.
PDB code: 1mem
9354234 N.Schaschke, I.Assfalg-Machleidt, W.Machleidt, D.Turk, and L.Moroder (1997).
E-64 analogues as inhibitors of cathepsin B. On the role of the absolute configuration of the epoxysuccinyl group.
  Bioorg Med Chem, 5, 1789-1797.  
8740363 M.Cygler, J.Sivaraman, P.Grochulski, R.Coulombe, A.C.Storer, and J.S.Mort (1996).
Structure of rat procathepsin B: model for inhibition of cysteine protease activity by the proregion.
  Structure, 4, 405-416.
PDB codes: 1mir 1mj6
8939744 M.R.Groves, M.A.Taylor, M.Scott, N.J.Cummings, R.W.Pickersgill, and J.A.Jenkins (1996).
The prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft.
  Structure, 4, 1193-1203.
PDB code: 1pci
  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 code is shown on the right.

 

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