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PDBsum entry 3d8v
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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 function of glmu from mycobacterium tuberculosis.
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Authors
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Z.Zhang,
E.M.Bulloch,
R.D.Bunker,
E.N.Baker,
C.J.Squire.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2009,
65,
275-283.
[DOI no: ]
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PubMed id
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Abstract
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Antibiotic resistance is a major issue in the treatment of infectious diseases
such as tuberculosis. Existing antibiotics target only a few cellular pathways
and there is an urgent need for antibiotics that have novel molecular
mechanisms. The glmU gene is essential in Mycobacterium tuberculosis, being
required for optimal bacterial growth, and has been selected as a possible drug
target for structural and functional investigation. GlmU is a bifunctional
acetyltransferase/uridyltransferase that catalyses the formation of UDP-GlcNAc
from GlcN-1-P. UDP-GlcNAc is a substrate for two important biosynthetic
pathways: lipopolysaccharide and peptidoglycan synthesis. The crystal structure
of M. tuberculosis GlmU has been determined in an unliganded form and in complex
with GlcNAc-1-P or UDP-GlcNAc. The structures reveal the residues that are
responsible for substrate binding. Enzyme activities were characterized by (1)H
NMR and suggest that the presence of acetyl-coenzyme A has an inhibitory effect
on uridyltransferase activity.
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Figure 3.
Figure 3 The uridyltransferase active site. (a) Binding of
GlcNAc-1-P (ball-and-stick model). Hydrogen bonds are shown as
dashed lines and the 2F[o] - F[c] electron density is contoured
at 1.0  .
(b) Comparison of GlcNAc-1-P (white outlined protein) and
UDP-GlcNAc (blue protein) binding and associated loop movement
within the uracil site. GlcNAc-1-P and UDP-GlcNAc molecules are
drawn as ball-and-stick models with white- and yellow-coloured C
atoms, respectively. Water molecules are drawn as red spheres
and are associated with the UDP-GlcNAc protein model.
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The above figure is
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2009,
65,
275-283)
copyright 2009.
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