PDBsum entry 2ce3

Hydrolase

PDB id: 2ce3

Contents

Protein chains

(+ 8 more) 167 a.a. *

Waters ×117

* Residue conservation analysis

PDB id:

2ce3

Name:

Hydrolase

Title:

Crystal structure of the atp-dependent clp protease proteolytic subunit 1 (clpp1) from mycobacterium tuberculosis

Structure:

Atp-dependent clp protease proteolytic subunit 1. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n. Synonym: endopeptidase clpp 1. Engineered: yes

Source:

Mycobacterium tuberculosis. Koch's bacillus. Organism_taxid: 83332. Strain: h37rv. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: institut pasteur collection

Biol. unit:

40mer (from PDB file)

Resolution:

2.60Å R-factor: 0.205 R-free: 0.261

Authors:

B.Segelke,C.Y.Kim,M.Ortiz-Lombardia,P.M.Alzari,T.Lekin

Key ref:

H.Ingvarsson et al. (2007). Insights into the inter-ring plasticity of caseinolytic proteases from the X-ray structure of Mycobacterium tuberculosis ClpP1. Acta Crystallogr D Biol Crystallogr, 63, 249-259. PubMed id: 17242518 DOI: 10.1107/S0907444906050530

Date:

03-Feb-06 Release date: 09-Feb-06

Protein chains

P9WPC5  (CLPP1_MYCTU) -  ATP-dependent Clp protease proteolytic subunit 1 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 200 a.a.

Struc: 167 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.21.92 - endopeptidase Clp.
• Reaction: Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are cleaved (such as succinyl-Leu-Tyr-|-NHMEC; and Leu-Tyr-Leu-|-Tyr-Trp, in which the cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp- bond also occurs).

DOI no: 10.1107/S0907444906050530

Acta Crystallogr D Biol Crystallogr 63:249-259 (2007)

PubMed id: 17242518

Insights into the inter-ring plasticity of caseinolytic proteases from the X-ray structure of Mycobacterium tuberculosis ClpP1.

H.Ingvarsson, M.J.Maté, M.Högbom, D.Portnoï, N.Benaroudj, P.M.Alzari, M.Ortiz-Lombardía, T.Unge.

ABSTRACT

Mycobacterium tuberculosis caseinolytic protease ClpP1 (Mt ClpP1) is a self-compartmentalized protease consisting of two heptameric rings stacked on top of each other, thus enclosing a catalytic chamber. Within the chamber, which can be reached through two axial pores, each of the 14 identical monomers possesses a serine protease active site. The unfolding and translocation of substrates into the chamber are mediated by associated hexameric ATPases covering the axial pores. Three crystal structures of Mt ClpP1, determined by molecular replacement, are presented in this study. Two of the models were refined to a resolution of 2.6 A and the third to 3.0 A. It was found that disorder in the handle domain affects the formation and configuration of the tetradecamer and results in condensed structures with larger equatorial pores when compared with ClpPs from other species. Additionally, this disorder accompanies conformational changes of the residues in the catalytic triad. The models also reveal structural differences within the N-terminal hairpin-loop domain, which possibly reflect the significant differences in amino-acid sequence between Mt ClpP1 and other ClpP homologues in this region.

Selected figure(s)

Figure 2.
Figure 2 Structure of the Mt ClpP1 monomer. (a) Ribbon-diagram representation, with labelling of the secondary-structure elements according to the structure of Ec ClpP1 (Wang et al., 1997[Wang, J., Hartling, J. A. & Flanagan, J. M. (1997). Cell, 91, 447-456.]). The chain is coloured from blue to red from the N-terminus to the C-terminus. The catalytic triad (Ser98, His123 and Asp172) is shown in stick representation. (b) A comparison of the C^ backbone of ClpP monomers corresponding to Mt (blue), Sp (green), Ec (gold), Pf (violet) and Hs (red). Amino acids from the head domains (residues 28-124 and 160-190 in Mt ClpP1) were selected for superimposition. (c) A 90°-rotated view from (b) showing a significant shift of the E helix in the handle domain of the Mt ClpP1 monomer.

Figure 4.
Figure 4 Properties of the Mt ClpP1 tetradecamer. (a) Superimposition of one heptamer from the Ec ClpP structure 1yg6 (molecular surface, gold) onto the heptamer of Mt ClpP1 structure 2cby (ribbons, blue) shows the greater compactness of the latter. (b) Superimposition of monomer A of the Ec ClpP structure 1yg6 onto monomer A of the Mt ClpP1 structure 2cby . The superimposed monomers are on the right of the represented heptamers. The colour scheme is as in (a). (c) Inwards rotation of the monomers of Mt ClpP1 shown by overlaying monomer A from (a) and (b). The axis of this rotation (in red) is approximately perpendicular to the pore axis (in green). (d) Side view of the front half surface of a complete model of Mt ClpP1, i.e. including the region Leu126-Asp135, to illustrate the equatorial pores. See text for details.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2007, 63, 249-259) copyright 2007.

Figures were selected by the author.