PDBsum entry 2c0y

Hydrolase

PDB id: 2c0y

Contents

Protein chain

308 a.a. *

Waters ×242

* Residue conservation analysis

PDB id:

2c0y

Name:

Hydrolase

Title:

The crystal structure of a cys25ala mutant of human procathepsin s

Structure:

Procathepsin s. Chain: a. Fragment: proenzyme, residues 17-331. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: testis. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five.

Resolution:

2.10Å R-factor: 0.198 R-free: 0.242

Authors:

G.Kaulmann,G.J.Palm,K.Schilling,R.Hilgenfeld,B.Wiederanders

Key ref:

G.Kaulmann et al. (2006). The crystal structure of a Cys25 -> Ala mutant of human procathepsin S elucidates enzyme-prosequence interactions. Protein Sci, 15, 2619-2629. PubMed id: 17075137 DOI: 10.1110/ps.062401806

Date:

08-Sep-05 Release date: 08-Nov-06

Protein chain

P25774  (CATS_HUMAN) -  Cathepsin S from Homo sapiens

Seq: 331 a.a.

Struc: 308 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.22.27 - cathepsin S.
• Reaction: Similar to cathepsin L, but with much less activity on Z-Phe-Arg-|-NHMec, and more activity on the Z-Val-Val-Arg-|-Xaa compound.

DOI no: 10.1110/ps.062401806

Protein Sci 15:2619-2629 (2006)

PubMed id: 17075137

The crystal structure of a Cys25 -> Ala mutant of human procathepsin S elucidates enzyme-prosequence interactions.

G.Kaulmann, G.J.Palm, K.Schilling, R.Hilgenfeld, B.Wiederanders.

ABSTRACT

The crystal structure of the active-site mutant Cys25 --> Ala of glycosylated human procathepsin S is reported. It was determined by molecular replacement and refined to 2.1 Angstrom resolution, with an R-factor of 0.198. The overall structure is very similar to other cathepsin L-like zymogens of the C1A clan. The peptidase unit comprises two globular domains, and a small third domain is formed by the N-terminal part of the prosequence. It is anchored to the prosegment binding loop of the enzyme. Prosegment residues beyond the prodomain dock to the substrate binding cleft in a nonproductive orientation. Structural comparison with published data for mature cathepsin S revealed that procathepsin S residues Phe146, Phe70, and Phe211 adopt different orientations. Being part of the S1' and S2 pockets, they may contribute to the selectivity of ligand binding. Regarding the prosequence, length, orientation and anchoring of helix alpha3p differ from related zymogens, thereby possibly contributing to the specificity of propeptide-enzyme interaction in the papain family. The discussion focuses on the functional importance of the most conserved residues in the prosequence for structural integrity, inhibition and folding assistance, considering scanning mutagenesis data published for procathepsin S and for its isolated propeptide.

Selected figure(s)

Figure 5.
Figure 5. Interaction of the prosegment (cathepsin S, dark gray; cathepsin K, light gray; color code for numbering and chain) with the

Figure 7.
Figure 7. C--H###p interactions between prosequence and active-site cleft

The above figures are reprinted by permission from the Protein Society: Protein Sci (2006, 15, 2619-2629) copyright 2006.

Figures were selected by an automated process.