PDBsum entry 2cio

Hydrolase/inhibitor

PDB id: 2cio

Contents

Protein chain

212 a.a. *

Ligands

GLY-GLY-THR

LEU-SER-LEU-ALA

GOL ×2

ACT ×3

Waters ×161

* Residue conservation analysis

PDB id:

2cio

Name:

Hydrolase/inhibitor

Title:

The high resolution x-ray structure of papain complexed with fragments of the trypanosoma brucei cysteine protease inhibitor icp.

Structure:

Papain. Chain: a. Synonym: papaya proteinase i, ppi, allergen, carp1papain. Inhibitor of cysteine peptidase. Chain: b. Synonym: cysteine protease inhibitor, icp. Engineered: yes. Other_details: two peptide fragments from digestion of icp

Source:

Carica papaya. Organism_taxid: 3649. Other_details: purchased from sigma. Trypanosoma brucei. Organism_taxid: 5691. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: c43.

Biol. unit:

Dimer (from PDB file)

Resolution:

1.50Å R-factor: 0.179 R-free: 0.225

Authors:

M.S.Alphey,W.N.Hunter

Key ref:

M.S.Alphey and W.N.Hunter (2006). High-resolution complex of papain with remnants of a cysteine protease inhibitor derived from Trypanosoma brucei. Acta Crystallograph Sect F Struct Biol Cryst Commun, 62, 504-508. PubMed id: 16754967 DOI: 10.1107/S1744309106014849

Date:

24-Mar-06 Release date: 18-May-06

Protein chain

P00784  (PAPA1_CARPA) -  Papain from Carica papaya

Seq: 345 a.a.

Struc: 212 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.22.2 - papain.
• 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'.

DOI no: 10.1107/S1744309106014849

Acta Crystallograph Sect F Struct Biol Cryst Commun 62:504-508 (2006)

PubMed id: 16754967

High-resolution complex of papain with remnants of a cysteine protease inhibitor derived from Trypanosoma brucei.

M.S.Alphey, W.N.Hunter.

ABSTRACT

Attempts to cocrystallize the cysteine protease papain derived from the latex of Carica papaya with an inhibitor of cysteine proteases (ICP) from Trypanosoma brucei were unsuccessful. However, crystals of papain that diffracted to higher resolution, 1.5 A, than other crystals of this archetypal cysteine protease were obtained, so the analysis was continued. Surprisingly, the substrate-binding cleft was occupied by two short peptide fragments which have been assigned as remnants of ICP. Comparisons reveal that these peptides bind in the active site in a manner similar to that of the human cysteine protease inhibitor stefin B when it is complexed to papain. The assignment of the fragment sequences is consistent with the specificity of the protease.

Selected figure(s)

Figure 1.
Figure 1 An omit difference electron-density map for Glu118 calculated with coefficients (F[o] - F[c]) and contoured at 3 (magenta) revealing the hydrogen-bonding (yellow dashed lines) pattern that defines the side-chain properties. F[o] and F[c] represent the observed and calculated structure factors, respectively. The refined model is shown in sticks with O atoms in red, N atoms in blue and C atoms in white. All figures were prepared using PyMOL (DeLano, 2002[DeLano, W. L. (2002). The PyMOL Molecular Graphics System. DeLano Scientific, San Carlos, CA, USA.]).

Figure 3.
Figure 3 Selected active-site details. Putative hydrogen-bonding interactions (green dashed lines) between papain (sticks coloured C black, O red, N blue, S yellow) and the peptide fragments derived from TbICP (sticks coloured C orange, O red, N blue) are depicted. The OD1, OD2 and OD3 atoms associated with the sulfonic acid group of Cys25 are labelled 1, 2 and 3, respectively; water molecules are shown as red spheres and labelled W.

The above figures are reprinted from an Open Access publication published by the IUCr: Acta Crystallograph Sect F Struct Biol Cryst Commun (2006, 62, 504-508) copyright 2006.

Figures were selected by the author.