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PDBsum entry 4q2k
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Hydrolase/hydrolase inhibitor
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PDB id
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4q2k
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PDB id:
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| Name: |
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Hydrolase/hydrolase inhibitor
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Title:
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Bovine alpha chymotrypsin bound to a cyclic peptide inhibitor, 5b
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Structure:
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Chymotrypsinogen a. Chain: a, b, c, d. Synonym: chymotrypsin a chain a, chymotrypsin a chain b, chymotrypsin a chain c. Ec: 3.4.21.1
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Source:
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Bos taurus. Bovine. Organism_taxid: 9913
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Resolution:
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2.20Å
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R-factor:
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0.209
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R-free:
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0.268
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Authors:
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H.Y.Chan,J.B.Bruning,A.D.Abell
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Key ref:
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K.C.Chua
et al.
(2014).
Macrocyclic protease inhibitors with reduced peptide character.
Angew Chem Int Ed Engl,
53,
7828-7831.
PubMed id:
DOI:
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Date:
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09-Apr-14
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Release date:
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23-Jul-14
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PROCHECK
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Headers
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References
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P00766
(CTRA_BOVIN) -
Chymotrypsinogen A from Bos taurus
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Seq:
Struc:
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245 a.a.
231 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.4.21.1
- chymotrypsin.
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Reaction:
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Preferential cleavage: Tyr-|-Xaa, Trp-|-Xaa, Phe-|-Xaa, Leu-|-Xaa.
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DOI no:
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Angew Chem Int Ed Engl
53:7828-7831
(2014)
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PubMed id:
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Macrocyclic protease inhibitors with reduced peptide character.
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K.C.Chua,
M.Pietsch,
X.Zhang,
S.Hautmann,
H.Y.Chan,
J.B.Bruning,
M.Gütschow,
A.D.Abell.
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ABSTRACT
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There is a real need for simple structures that define a β-strand conformation,
a secondary structure that is central to peptide-protein interactions. For
example, protease substrates and inhibitors almost universally adopt this
geometry on active site binding. A planar pyrrole is used to replace two amino
acids of a peptide backbone to generate a simple macrocycle that retains the
required geometry for active site binding. The resulting β-strand templates
have reduced peptide character and provide potent protease inhibitors with the
attachment of an appropriate amino aldehyde to the C-terminus. Picomolar
inhibitors of cathepsin L and S are reported and the mode of binding of one
example to the model protease chymotrypsin is defined by X-ray crystallography.
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Links
