PDBsum entry 1pci

Thiol protease

PDB id: 1pci

Contents

Protein chains

311 a.a. *

* Residue conservation analysis

PDB id:

1pci

Name:

Thiol protease

Title:

Procaricain

Structure:

Procaricain. Chain: a, b, c. Synonym: pro papaya protease omega. Engineered: yes. Mutation: yes. Other_details: active site his mutation

Source:

Carica papaya. Papaya. Organism_taxid: 3649. Tissue: leaf. Gene: omega. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.20Å R-factor: 0.226 R-free: 0.286

Authors:

M.R.Groves,M.A.J.Taylor,M.Scott,N.J.Cummings,R.W.Pickersgill, J.A.Jenkins

Key ref:

M.R.Groves et al. (1996). The prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft. Structure, 4, 1193-1203. PubMed id: 8939744 DOI: 10.1016/S0969-2126(96)00127-X

Date:

28-Jun-96 Release date: 01-Apr-97

Protein chains

P10056  (PAPA3_CARPA) -  Caricain from Carica papaya

Seq: 348 a.a.

Struc: 311 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.4.22.30 - caricain.
• Reaction: Hydrolysis of proteins with broad specificity for peptide bonds, similar to those of papain and chymopapain.

DOI no: 10.1016/S0969-2126(96)00127-X

Structure 4:1193-1203 (1996)

PubMed id: 8939744

The prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft.

M.R.Groves, M.A.Taylor, M.Scott, N.J.Cummings, R.W.Pickersgill, J.A.Jenkins.

ABSTRACT

BACKGROUND: Cysteine proteases are involved in a variety of cellular processes including cartilage degradation in arthritis, the progression of Alzheimer's disease and cancer invasion: these enzymes are therefore of immense biological importance. Caricain is the most basic of the cysteine proteases found in the latex of Carica papaya. It is a member of the papain superfamily and is homologous to other plant and animal cysteine proteases. Caricain is naturally expressed as an inactive zymogen called procaricain. The inactive form of the protease contains an inhibitory proregion which consists of an additional 106 N-terminal amino acids; the proregion is removed upon activation. RESULTS: The crystal structure of procaricain has been refined to 3.2 A resolution; the final model consists of three non-crystallographically related molecules. The proregion of caricain forms a separate globular domain which binds to the C-terminal domain of mature caricain. The proregion also contains an extended polypeptide chain which runs through the substrate-binding cleft, in the opposite direction to that of the substrate, and connects to the N terminus of the mature region. The mature region does not undergo any conformational change on activation. CONCLUSIONS: We conclude that the rate-limiting step in the in vitro activation of procaricain is the dissociation of the prodomain, which is then followed by proteolytic cleavage of the extended polypeptide chain of the proregion. The prodomain provides a stable scaffold which may facilitate the folding of the C-terminal lobe of procaricain.

Selected figure(s)

Figure 7.
Figure 7. A diagram showing the proregion as it passes through the substrate-binding cleft. The proregion is shown in ball-and-stick representation and caricain is depicted as a molecular surface representation; the most negative potentials are shown in red, the most positive are in blue. The position of Gly84p is indicated by the black arrow. The C-terminal domain of caricain is towards the top of the picture and the position of Asp158 is indicated. The surface is contoured at ± 12.5eV. (Figure produced using GRASP [40].)

The above figure is reprinted by permission from Cell Press: Structure (1996, 4, 1193-1203) copyright 1996.

Figure was selected by an automated process.