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PDBsum entry 3a3d
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References listed in PDB file
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Key reference
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Title
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Crystal structures of penicillin-Binding proteins 4 and 5 from haemophilus influenzae.
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Authors
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F.Kawai,
T.B.Clarke,
D.I.Roper,
G.J.Han,
K.Y.Hwang,
S.Unzai,
E.Obayashi,
S.Y.Park,
J.R.Tame.
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Ref.
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J Mol Biol, 2010,
396,
634-645.
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PubMed id
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Abstract
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We have determined high-resolution apo crystal structures of two low molecular
weight penicillin-binding proteins (PBPs), PBP4 and PBP5, from Haemophilus
influenzae, one of the most frequently found pathogens in the upper respiratory
tract of children. Novel beta-lactams with notable antimicrobial activity have
been designed, and crystal structures of PBP4 complexed with ampicillin and two
of the novel molecules have also been determined. Comparing the apo form with
those of the complexes, we find that the drugs disturb the PBP4 structure and
weaken X-ray diffraction, to very different extents. PBP4 has recently been
shown to act as a sensor of the presence of penicillins in Pseudomonas
aeruginosa, and our models offer a clue to the structural basis for this effect.
Covalently attached penicillins press against a phenylalanine residue near the
active site and disturb the deacylation step. The ready inhibition of PBP4 by
beta-lactams compared to PBP5 also appears to be related to the weaker
interactions holding key residues in a catalytically competent position.
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