PDBsum entry 1k3b

Hydrolase

PDB id: 1k3b

Contents

Protein chains

119 a.a. *

164 a.a. *

69 a.a. *

Ligands

NAG

SO4 ×3

Metals

_CL

Waters ×464

* Residue conservation analysis

PDB id:

1k3b

Name:

Hydrolase

Title:

Crystal structure of human dipeptidyl peptidase i (cathepsin c): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases

Structure:

Dipeptydil-peptidase i exclusion domain. Chain: a. Synonym: dppi, cathepsin c, residual propart. Engineered: yes. Dipeptydil-peptidase i light chain. Chain: b. Synonym: dppi, cathepsin c, beta chain. Engineered: yes. Dipeptydil-peptidase i heavy chain.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five. Expression_system_cell: insect cell(invitrogen).

Biol. unit:

Dodecamer (from PDB file)

Resolution:

2.15Å R-factor: 0.190 R-free: 0.231

Authors:

D.Turk,V.Janjic,I.Stern,M.Podobnik,D.Lamba,S.W.Dahl,C.Lauritzen, J.Pedersen,V.Turk,B.Turk

Key ref:

D.Turk et al. (2001). Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. Embo J, 20, 6570-6582. PubMed id: 11726493 DOI: 10.1093/emboj/20.23.6570

Date:

02-Oct-01 Release date: 02-Apr-02

Protein chain

P53634  (CATC_HUMAN) -  Dipeptidyl peptidase 1 from Homo sapiens

Seq: 463 a.a.

Struc: 119 a.a.

Protein chain

P53634  (CATC_HUMAN) -  Dipeptidyl peptidase 1 from Homo sapiens

Seq: 463 a.a.

Struc: 164 a.a.

Protein chain

P53634  (CATC_HUMAN) -  Dipeptidyl peptidase 1 from Homo sapiens

Seq: 463 a.a.

Struc: 69 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C: E.C.3.4.14.1 - dipeptidyl-peptidase I.
• Reaction: Release of an N-terminal dipeptide, Xaa-Xbb-|-Xcc, except when Xaa is Arg or Lys, or Xbb or Xcc is Pro.

DOI no: 10.1093/emboj/20.23.6570

Embo J 20:6570-6582 (2001)

PubMed id: 11726493

Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases.

D.Turk, V.Janjić, I.Stern, M.Podobnik, D.Lamba, S.W.Dahl, C.Lauritzen, J.Pedersen, V.Turk, B.Turk.

ABSTRACT

Dipeptidyl peptidase I (DPPI) or cathepsin C is the physiological activator of groups of serine proteases from immune and inflammatory cells vital for defense of an organism. The structure presented shows how an additional domain transforms the framework of a papain-like endopeptidase into a robust oligomeric protease-processing enzyme. The tetrahedral arrangement of the active sites exposed to solvent allows approach of proteins in their native state; the massive body of the exclusion domain fastened within the tetrahedral framework excludes approach of a polypeptide chain apart from its termini; and the carboxylic group of Asp1 positions the N-terminal amino group of the substrate. Based on a structural comparison and interactions within the active site cleft, it is suggested that the exclusion domain originates from a metallo-protease inhibitor. The location of missense mutations, characterized in people suffering from Haim-Munk and Papillon-Lefevre syndromes, suggests how they disrupt the fold and function of the enzyme.

Selected figure(s)

Figure 3.
Figure 3 Active site cleft of DPPI with a bound model of the N-terminal sequence ERIIGG from the biological substrate, granzyme A. (A) Stereo view: covalent bonds of papain-like domains and the exclusion domain are shown in the colors used in Figure 1C. Covalent bonds of the substrate model are shown as yellow sticks. Corresponding carbon atoms are shown as balls using the covalent bond color scheme. The chloride ion is shown as a large green sphere. Oxygen, nitrogen and sulfur atoms are shown as red, blue and yellow spheres, respectively. The residues relevant for substrate binding are marked and hydrogen bonds are shown as white broken lines. The molecular surface was generated with GRASP (Nicholls et al., 1991); the figure was prepared in MAIN (Turk, 1992) and rendered with RENDER (Merritt and Bacon, 1997). (B) Schematic presentation. The color codes are the same as in (A).

Figure 4.
Figure 4 Features of papain-like exopeptidases. A view towards the active site clefts of superimposed papain-like proteases. The underlying molecular surface of cathepsin L, shown in white, is used to demonstrate an endopeptidase active site cleft, which is blocked by features of the exopeptidase structures. The surface of the catalytic cysteine is colored in yellow. Chain traces of cathepsins B, X and H are shown in green, cyan and purple, respectively. Chain traces of papain-like domains of DPPI are shown in dark blue, whereas for the chain trace of the exclusion domain the color code is the same as in Figure 1. The bleomycin hydrolase chain trace is not shown for reasons of clarity, although its C-terminal residues superimpose almost perfectly with the C-terminal residues of the cathepsin H mini-chain (purple).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Embo J (2001, 20, 6570-6582) copyright 2001.

Figures were selected by an automated process.