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PDBsum entry 1jtd
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Hydrolase/inhibitor
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PDB id
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1jtd
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Contents |
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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 and kinetic analysis of beta-Lactamase inhibitor protein-Ii in complex with tem-1 beta-Lactamase.
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Authors
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D.Lim,
H.U.Park,
L.De castro,
S.G.Kang,
H.S.Lee,
S.Jensen,
K.J.Lee,
N.C.Strynadka.
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Ref.
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Nat Struct Biol, 2001,
8,
848-852.
[DOI no: ]
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PubMed id
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Abstract
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The structure of the 28 kDa beta-lactamase inhibitor protein-II (BLIP-II) in
complex with the TEM-1 beta-lactamase has been determined to 2.3 A resolution.
BLIP-II is a secreted protein produced by the soil bacterium Streptomyces
exfoliatus SMF19 and is able to bind and inhibit TEM-1 with subnanomolar
affinity. BLIP-II is a seven-bladed beta-propeller with a unique blade motif
consisting of only three antiparallel beta-strands. The overall fold is highly
similar to the core structure of the human regulator of chromosome condensation
(RCC1). Although BLIP-II does not share the same fold with BLIP, the first
beta-lactamase inhibitor protein for which structural data was available, a
comparison of the two complexes reveals a number of similarities and provides
further insights into key components of the TEM-1-BLIP and TEM-1-BLIP-II
interfaces. Our preliminary results from gene knock-out studies and scanning
electron microscopy also reveal a critical role of BLIP-II in sporulation.
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Figure 3.
Figure 3. TEM-1 -BLIP interface. a, BLIP (blue) binds
competitively to TEM-1 (orange). BLIP has an overall  -saddle
fold consisting of two tandem repeats. The large concave
eight-stranded -sheet
of BLIP wraps around the TEM-1 loop-helix region (green). Asp 49
and Phe 142 on the protruding -hairpin
turns of BLIP insert into the TEM-1 active site cavity and
structurally mimic the carboxylate and benzyl side chain of a
penicillin substrate. To illustrate the competitive mode of
inhibition, the penicilloyl moiety (thin stick rendering) of the
TEM-1 -penicillin G acyl-enzyme intermediate^13 is superimposed
on the active site region of the complex. b, Interface between
BLIP (blue) and the TEM-1 loop-helix region (residues 99 -114
shown in stick rendering with green carbons). For clarity, the
side chains of Asp 101, Thr 109 and His 112 on TEM-1 were
omitted.
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Figure 4.
Figure 4. Scanning electron micrographs of Streptomyces
exfoliatus SMF19 cells. a, Spore formation by septation of
wild type hyphae. b, The absence of sporulation in a BLIP-II
knock-out mutant produces the so-called 'bald' phenotype. c,
Comparison of the structures of TEM-1 -lactamase
(orange) and the Streptomyces K15 penicillin binding protein
(K15 PBP)30 (blue), highlighting the overall structural
similarities. The region in TEM-1 to which BLIP-II binds is
colored green, as is the structurally equivalent region in the
K15 PBP. The active site Ser-Lys dyads are shown as
ball-and-stick renderings.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2001,
8,
848-852)
copyright 2001.
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