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PDBsum entry 1mr2
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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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Structure and mechanism of mt-Adprase, A nudix hydrolase from mycobacterium tuberculosis.
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Authors
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L.W.Kang,
S.B.Gabelli,
J.E.Cunningham,
S.F.O'Handley,
L.M.Amzel.
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Ref.
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Structure, 2003,
11,
1015-1023.
[DOI no: ]
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PubMed id
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Abstract
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Nudix hydrolases are a family of proteins that contain the characteristic
sequence GX(5)EX(7)REUXEEXG(I/L/V), the Nudix box. They catalyze the hydrolysis
of a variety of nucleoside diphosphate derivatives such as ADP-ribose, Ap(n)A (3
</= n </= 6), NADH, and dATP. A number of Nudix hydrolases from several
species, ranging from bacteria to humans, have been characterized, including, in
some cases, the determination of their three-dimensional structures. The product
of the Rv1700 gene of M. tuberculosis is a Nudix hydrolase specific for
ADP-ribose (ADPR). We have determined the crystal structures of MT-ADPRase
alone, and in complex with substrate, with substrate and the nonactivating metal
ion Gd(3+), and in complex with a nonhydrolyzable ADPR analog and the activating
metal ion Mn(2+). These structures, refined with data extending to resolutions
between 2.0 and 2.3 A, showed that there are sequence differences in binding
site residues between MT-ADPRase and a human homolog that may be exploited for
antituberculosis drug development.
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Figure 5.
Figure 5. Recognition of the Nonhydrolyzable Substrate
Analog, AMPCPR, and Three Mn2+ Ions by MT-ADPRase(A) Schematic
representation. Residue 142 is from loop L9 that is not ordered
without three manganese ions and AMPCPR.(B) Stereo diagram of
the ADP-ribose binding site with AMPCPR and three manganese
ions. Residues and substrate are shown using the same
representation and color scheme of Figure 4A. Broken orange
lines represent polar interactions among AMPCPR, three manganese
ions, and protein residues.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2003,
11,
1015-1023)
copyright 2003.
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