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PDBsum entry 3l1v
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References listed in PDB file
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Key reference
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Title
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Structural and kinetic characterization of the lps biosynthetic enzyme d-Alpha,Beta-D-Heptose-1,7-Bisphosphate phosphatase (gmhb) from escherichia coli.
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Authors
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P.L.Taylor,
S.Sugiman-Marangos,
K.Zhang,
M.A.Valvano,
G.D.Wright,
M.S.Junop.
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Ref.
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Biochemistry, 2010,
49,
1033-1041.
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PubMed id
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Abstract
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Lipopolysaccharide is a major component of the outer membrane of gram-negative
bacteria and provides a permeability barrier to many commonly used antibiotics.
ADP-heptose residues are an integral part of the LPS inner core, and mutants
deficient in heptose biosynthesis demonstrate increased membrane permeability.
The heptose biosynthesis pathway involves phosphorylation and dephosphorylation
steps not found in other pathways for the synthesis of nucleotide sugar
precursors. Consequently, the heptose biosynthetic pathway has been marked as a
novel target for antibiotic adjuvants, which are compounds that facilitate and
potentiate antibiotic activity. D-alpha,beta-D-heptose-1,7-bisphosphate
phosphatase (GmhB) catalyzes the third essential step of LPS heptose
biosynthesis. This study describes the first crystal structure of GmhB and
enzymatic analysis of the protein. Structure-guided mutations followed by steady
state kinetic analysis, together with established precedent for HAD
phosphatases, suggest that GmhB functions through a phosphoaspartate
intermediate. This study provides insight into the structure-function
relationship of GmhB, a new target for combatting gram-negative bacterial
infection.
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