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PDBsum entry 4m6h
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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 biochemical analyses of mycobacterium tuberculosis n-Acetylmuramyl-L-Alanine amidase rv3717 point to a role in peptidoglycan fragment recycling.
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Authors
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D.M.Prigozhin,
D.Mavrici,
J.P.Huizar,
H.J.Vansell,
T.Alber.
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Ref.
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J Biol Chem, 2013,
288,
31549-31555.
[DOI no: ]
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PubMed id
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Abstract
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Peptidoglycan hydrolases are key enzymes in bacterial cell wall homeostasis.
Understanding the substrate specificity and biochemical activity of
peptidoglycan hydrolases in Mycobacterium tuberculosis is of special interest as
it can aid in the development of new cell wall targeting therapeutics. In this
study, we report biochemical and structural characterization of the
mycobacterial N-acetylmuramyl-l-alanine amidase, Rv3717. The crystal structure
of Rv3717 in complex with a dipeptide product shows that, compared with
previously characterized peptidoglycan amidases, the enzyme contains an extra
disulfide-bonded β-hairpin adjacent to the active site. The structure of two
intermediates in assembly reveal that Zn(2+) binding rearranges active site
residues, and disulfide formation promotes folding of the β-hairpin. Although
Zn(2+) is required for hydrolysis of muramyl dipeptide, disulfide oxidation is
not required for activity on this substrate. The orientation of the product in
the active site suggests a role for a conserved glutamate (Glu-200) in
catalysis; mutation of this residue abolishes activity. The product binds at the
head of a closed tunnel, and the enzyme showed no activity on polymerized
peptidoglycan. These results point to a potential role for Rv3717 in
peptidoglycan fragment recycling.
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