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PDBsum entry 2c8t
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References listed in PDB file
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Key reference
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Title
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Insights into the inter-Ring plasticity of caseinolytic proteases from the X-Ray structure of mycobacterium tuberculosis clpp1.
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Authors
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H.Ingvarsson,
M.J.Maté,
M.Högbom,
D.Portnoï,
N.Benaroudj,
P.M.Alzari,
M.Ortiz-Lombardía,
T.Unge.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2007,
63,
249-259.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2007,
63,
249-259)
copyright 2007.
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