PDBsum entry: 1glo

Hydrolase

PDB id: 1glo

Contents

Protein chain

217 a.a. *

Waters ×173

* Residue conservation analysis

PDB id:

1glo

Name:

Hydrolase

Title:

Crystal structure of cys25ser mutant of human cathepsin s

Structure:

Cathepsin s. Chain: a. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

2.2Å R-factor: 0.196 R-free: 0.253

Authors:

J.P.Turkenburg,M.B.A.C.Lamers,A.M.Brzozowski,L.M.Wright, R.E.Hubbard,S.L.Sturt,D.H.Williams

Key ref:

J.P.Turkenburg et al. (2002). Structure of a Cys25-->Ser mutant of human cathepsin S. Acta Crystallogr D Biol Crystallogr, 58, 451-455. PubMed id: 11856830 DOI: 10.1107/S0907444901021825

Date:

31-Aug-01 Release date: 29-Aug-02

Protein chain

P25774  (CATS_HUMAN) -  Cathepsin S

Seq: 331 a.a.

Struc: 217 a.a.*

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

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.

 Gene Ontology (GO) functional annotation 

• Biological process: proteolysis (1 term)
• Biochemical function: cysteine-type peptidase activity (2 terms)

DOI no: 10.1107/S0907444901021825

Acta Crystallogr D Biol Crystallogr 58:451-455 (2002)

PubMed id: 11856830

Structure of a Cys25-->Ser mutant of human cathepsin S.

J.P.Turkenburg, M.B.Lamers, A.M.Brzozowski, L.M.Wright, R.E.Hubbard, S.L.Sturt, D.H.Williams.

ABSTRACT

Cathepsin S (EC 3.4.22.27), a cysteine proteinase of the papain superfamily, plays a critical role in the generation of a major histocompatibility complex (MHC) class II restricted T-cell response by antigen-presenting cells. Therefore, selective inhibition of this enzyme may be useful in modulating class II restricted T-cell responses in immune-related disorders such as rheumatoid arthritis, multiple sclerosis and extrinsic asthma. The three-dimensional structure at 2.2 A resolution of the active-site Cys25-->Ser mutant presented here in an unliganded state provides further insight useful for the design of selective enzyme inhibitors.

Selected figure(s)

Figure 2.
Figure 2 Superposition of the active-site residues of mutant cathepsin S (in red) and cathepsin K (in yellow). The hydrogen-bonding network for the mutant enzyme is shown. The catalytic triad (with the Ser25 mutation) is shown on the right, with three water molecules in the centre and Gln19 and Trp186 to the left. Hydrogen bonds are shown as dashed lines. The observed network may provide a mechanism for correct catalytic residue side-chain orientation prior to substrate hydrolysis. Also shown is the final maximum-likelihood-weighted electron-density map (2F[o] - F[c]), contoured at 1 above the mean. This figure shows convincingly that the constellation of the active-site residues is essentially unchanged in the mutant.

The above figure is reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2002, 58, 451-455) copyright 2002.

Figure was selected by an automated process.