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PDBsum entry 1r88
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Immune system
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PDB id
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1r88
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The structure of mycobacterium tuberculosis mpt51 (fbpc1) defines a new family of non-Catalytic alpha/beta hydrolases.
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Authors
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R.A.Wilson,
W.N.Maughan,
L.Kremer,
G.S.Besra,
K.Fütterer.
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Ref.
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J Mol Biol, 2004,
335,
519-530.
[DOI no: ]
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PubMed id
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Abstract
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Mycobacterium tuberculosis, the causative agent of tuberculosis, is known to
secrete a number of highly immunogenic proteins that are thought to confer
pathogenicity, in part, by mediating binding to host tissues. Among these
secreted proteins are the trimeric antigen 85 (Ag85) complex and the related
MPT51 protein, also known as FbpC1. While the physiological function of Ag85, a
mycolyltransferase required for the biosynthesis of the cell wall component
alpha,alpha'-trehalose dimycolate (or cord factor), has been identified
recently, the function of the closely related MPT51 (approximately 40% identity
with the Ag85 components) remains to be established. The crystal structure of
M.tuberculosis MPT51, determined to 1.7 A resolution, shows that MPT51, like the
Ag85 components Ag85B and Ag85C2, folds as an alpha/beta hydrolase, but it does
not contain any of the catalytic elements required for mycolyltransferase
activity. Moreover, the absence of a recognizable alpha,alpha'-trehalose
monomycolate-binding site and the failure to detect an active site suggest that
the function of MPT51 is of a non-enzymatic nature and that MPT51 may in fact
represent a new family of non-catalytic alpha/beta hydrolases. Previous
experimental evidence and the structural similarity to some integrins and
carbohydrate-binding proteins led to the hypothesis that MPT51 might have a role
in host tissue attachment, whereby ligands may include the serum protein
fibronectin and small sugars.
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Figure 2.
Figure 2. Stereo views of the tertiary structure of MPT51,
the structural superimposition with Ag85C2 and of the "active
site". (a) Secondary structure is color-coded: green, b-sheet;
cyan, a-helix; dark blue, 3[10] helix. The residues
corresponding to the catalytic triad in the Ag85 subunits are
shown as rods (yellow, carbon; blue, nitrogen; red, oxygen). (b)
Illustration of structural differences between MPT51 and Ag85C2.
Ribbon in light and dark blue corresponds to the active and
inhibitor-bound forms of Ag85C2. The b7-a9 loop and helix a9 of
MPT51 is shown in red, the fibronectin-binding loop in green.
(c) Electron density (s[A]-weighted 2F[o] -F[c] map, 30-1.7
Å, after automatic backbone tracing in ARP/wARP, contour
level 1.2s) of the active site of MPT51 with the catalytic triad
of Ag85C2 superimposed (rods in light blue). The final refined
model of MPT51 is shown with rods color-coded as in (a). The
Figure was prepared using RIBBONS.[53.]
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Figure 3.
Figure 3. (a) Stereo view of cavities in Ag85C2 (gray)
versus MPT51 (cyan) superimposed with the ribbon diagram of
MPT51. The trehalose molecule of the structure of Ag85B[20.] is
shown as a guide for the eye. (b) Stereo view of the
superimposition of the structures of the effector domain of E.
coli TreR[37.] (blue) and of the S. typhimurium
glucose/galactose receptor[38.] (green) with MPT51 (gray). The
trehalose-6-phosphate ligand of TreR (red rods) and the
trehalose molecule (yellow) of the Ag85B structure are shown.
(c) and (d) Surface diagrams of (c) MPT51 and (d) Ag85B colored
according to sequence conservation (red=identity). The surface
area corresponding to the fibronectin-binding loop is marked in
green. The Figure was prepared using (a) SURFNET, [28.] (a) and
(b) RIBBONS [53.] and (c) GRASP. [54.]
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2004,
335,
519-530)
copyright 2004.
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