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PDBsum entry 4zfq
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References listed in PDB file
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Key reference
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Title
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Loss of a functionally and structurally distinct ld-Transpeptidase, Ldtmt5, Compromises cell wall integrity in mycobacterium tuberculosis.
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Authors
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L.A.Brammer basta,
A.Ghosh,
Y.Pan,
J.Jakoncic,
E.P.Lloyd,
C.A.Townsend,
G.Lamichhane,
M.A.Bianchet.
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Ref.
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J Biol Chem, 2015,
290,
25670-25685.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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The final step of peptidoglycan (PG) biosynthesis in bacteria involves
cross-linking of peptide side chains. This step in Mycobacterium tuberculosis is
catalyzed by ld- and dd-transpeptidases that generate 3→3 and 4→3
transpeptide linkages, respectively. M. tuberculosis PG is predominantly 3→3
cross-linked, and LdtMt2 is the dominant ld-transpeptidase. There are four
additional sequence paralogs of LdtMt2 encoded by the genome of this pathogen,
and the reason for this apparent redundancy is unknown. Here, we studied one of
the paralogs, LdtMt5, and found it to be structurally and functionally distinct.
The structures of apo-LdtMt5 and its meropenem adduct presented here demonstrate
that, despite overall architectural similarity to LdtMt2, the LdtMt5 active site
has marked differences. The presence of a structurally divergent catalytic site
and a proline-rich C-terminal subdomain suggest that this protein may have a
distinct role in PG metabolism, perhaps involving other cell wall-anchored
proteins. Furthermore, M. tuberculosis lacking a functional copy of LdtMt5
displayed aberrant growth and was more susceptible to killing by crystal violet,
osmotic shock, and select carbapenem antibiotics. Therefore, we conclude that
LdtMt5 is not a functionally redundant ld-transpeptidase, but rather it serves a
unique and important role in maintaining the integrity of the M. tuberculosis
cell wall.
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Secondary reference #1
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Title
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Targeting the cell wall of mycobacterium tuberculosis: structure and mechanism of l,D-Transpeptidase 2.
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Authors
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S.B.Erdemli,
R.Gupta,
W.R.Bishai,
G.Lamichhane,
L.M.Amzel,
M.A.Bianchet.
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Ref.
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Structure, 2012,
20,
2103-2115.
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PubMed id
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