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PDBsum entry 1pfg
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Hydrolase/hydrolase inhibitor
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PDB id
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1pfg
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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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Strategy to design peptide inhibitors: structure of a complex of proteinase k with a designed octapeptide inhibitor n-Ac-Pro-Ala-Pro-Phe-Dala-Ala-Ala-Ala-Nh2 at 2.5 a resolution.
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Authors
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A.K.Saxena,
T.P.Singh,
K.Peters,
S.Fittkau,
C.Betzel.
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Ref.
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Protein Sci, 1996,
5,
2453-2458.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of a complex formed by the interaction between proteinase
K and a designed octapeptide amide, N-Ac-Pro-Ala-Pro-Phe-DAla-Ala-Ala-Ala-NH2,
has been determined at 2.5 A resolution and refined to an R-factor of 16.7% for
7,430 reflections in the resolution range of 8.0-2.50 A. The inhibitor forms a
stable complex through a series of hydrogen bonds and hydrophobic interactions
with the protein atoms and water molecules. The inhibitor is hydrolyzed between
Phe4I and DAla5I (I indicates the inhibitor). The two fragments are separated by
a distance of 3.2 A between the carbonyl carbon of Phe4I and the main-chain
nitrogen of DAla5I. The N-terminal tetrapeptide occupies subsites S1-S5 (S5 for
acetyl group), whereas the C-terminal part fits into S1'-S5' region (S5' for
amide group). It is the first time that such an extended electron density for a
designed synthetic peptide inhibitor has been observed in the prime region of an
enzyme of the subtilisin family. In fact, the inhibitor fills the recognition
site completely. There is only a slight rearrangement of the protein residues to
accommodate the inhibitor. Superposition of the present octapeptide inhibitor on
the hexapeptide inhibitor studied previously shows an overall homology of the
two inhibitors, although the individual atoms are displaced significantly. It
suggests the existence of a recognition site with flexible dimensions. Kinetic
studies indicate an inhibition rate of 100% by this specifically designed
peptide inhibitor.
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