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PDBsum entry 2sec
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Complex(serine proteinase-inhibitor)
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PDB id
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2sec
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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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Structural comparison of two serine proteinase-Protein inhibitor complexes: eglin-C-Subtilisin carlsberg and ci-2-Subtilisin novo.
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Authors
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C.A.Mcphalen,
M.N.James.
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Ref.
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Biochemistry, 1988,
27,
6582-6598.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structures of the molecular complexes between two serine proteinases
and two of their protein inhibitors have been determined: subtilisin Carlsberg
with the recombinant form of eglin-c from the leech Hirudo medicinalis and
subtilisin Novo with chymotrypsin inhibitor 2 from barley seeds. The structures
have been fully refined by restrained-parameter least-squares methods to
crystallographic R factors (sigma[[Fo[ - [Fc[[/sigma[Fo[) of 0.136 at 1.8-A
resolution and 0.154 at 2.1-A resolution, respectively. The 274 equivalent
alpha-carbon atoms of the enzymes superpose with an rms deviation of 0.53 A.
Sequence changes between the enzymes result in localized structural adjustments.
Functional groups in the active sites superpose with an rms deviation of 0.19 A
for 161 equivalent atoms; this close similarity in the conformation of
active-site residues provides no obvious reason for known differences in
catalytic activity between Carlsberg and Novo. Conformational changes in the
active-site region indicate a small induced fit of enzyme and inhibitor. Some
conformational differences are observed between equivalent active-site residues
of subtilisin Carlsberg and alpha-chymotrypsin. Despite differences in tertiary
architecture, most enzyme-substrate (inhibitor) interactions are maintained.
Subtilisin Carlsberg has a rare cis-peptide bond preceding Thr211 (Gly211 in
Novo). Both enzymes contain tightly bound Ca2+ ions. Site 1 is heptacoordinate
with the oxygen atoms at the vertices of a pentagonal bipyramid. Site 2 in
Carlsberg is probably occupied by a K+ ion in Novo. Conserved water molecules
appear to play important structural roles in the enzyme interior, in the
inhibitor beta-sheet, and at the enzyme-inhibitor interface. The 62 equivalent
alpha-carbon atoms of the inhibitors superpose with an rms deviation of 1.68 A.
Sequence changes result in somewhat different packing of the alpha-helix,
beta-sheet, and reactive-site loop relative to each other. Hydrogen bonds and
electrostatic interactions supporting the conformation of the reactive-site loop
are conserved. The 24 main-chain plus C beta atoms of P4 to P1' overlap with an
rms deviation of 0.19 A. Features contributing to the inhibitory nature of
eglin-c and CI-2 are discussed.
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Secondary reference #1
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Title
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Crystal and molecular structure of the inhibitor eglin from leeches in complex with subtilisin carlsberg.
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Authors
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C.A.Mcphalen,
H.P.Schnebli,
M.N.James.
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Ref.
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Febs Lett, 1985,
188,
55-58.
[DOI no: ]
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PubMed id
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Figure 1.
Fig. 1. An a-carbon backbone drawing of eglin-c (thin
lines) complexed to subtilisin Carlsberg (thic lines).
Every 5th amino acid is labelled in he inhibitor, every
10th in the enzyme. n I follows the sequence number
of inhibitor residues to distinguish them from those of
the enzyme.
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The above figure is
reproduced from the cited reference
with permission from the Federation of European Biochemical Societies
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