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PDBsum entry 1b12
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Contents |
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239 a.a.
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211 a.a.
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226 a.a.
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222 a.a.
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* Residue conservation analysis
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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 structure of a bacterial signal peptidase in complex with a beta-Lactam inhibitor.
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Authors
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M.Paetzel,
R.E.Dalbey,
N.C.Strynadka.
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Ref.
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Nature, 1998,
396,
186-190.
[DOI no: ]
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PubMed id
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Abstract
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The signal peptidase (SPase) from Escherichia coli is a membrane-bound
endopeptidase with two amino-terminal transmembrane segments and a
carboxy-terminal catalytic region which resides in the periplasmic space. SPase
functions to release proteins that have been translocated into the inner
membrane from the cell interior, by cleaving off their signal peptides. We
report here the X-ray crystal structure of a catalytically active soluble
fragment of E. coli SPase (SPase delta2-75). We have determined this structure
at 1.9 A resolution in a complex with an inhibitor, a beta-lactam (5S,6S penem),
which is covalently bound as an acyl-enzyme intermediate to the gamma-oxygen of
a serine residue at position 90, demonstrating that this residue acts as the
nucleophile in the hydrolytic mechanism of signal-peptide cleavage. The
structure is consistent with the use by SPase of Lys 145 as a general base in
the activation of the nucleophilic Ser90, explains the specificity requirement
at the signal-peptide cleavage site, and reveals a large exposed hydrophobic
surface which could be a site for an intimate association with the membrane. As
enzymes that are essential for cell viability, bacterial SPases present a
feasible antibacterial target: our determination of the SPase structure
therefore provides a template for the rational design of antibiotic compounds.
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Figure 3.
Figure 3 Structure of the  -lactam-type
inhibitor allyl
(5S,6S)-6-[(R)-acetoxyethyl]penem-3-carboxylateup.4,5.
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Figure 5.
Figure 5 A ball-and-stick representation30 of the active-site
residues of SPase  2-75
with the P1-P4 residues of an acylated peptide substrate
(Ala-Ala-Ala-Ala) modelled into the bindings sites S1-S4. The
observed positions of the methyl group (C16) and the carbonyl
oxygen (O8) of the inhibitor (Fig. 4) were used as a guide.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(1998,
396,
186-190)
copyright 1998.
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