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PDBsum entry 5mfs
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PDB id:
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Hydrolase
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Title:
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The crystal structure of e. Coli aminopeptidase n in complex with 7- amino-4-phenyl-5,7,8,9-tetrahydrobenzocyclohepten-6-one
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Structure:
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Aminopeptidase n. Chain: a. Synonym: alpha-aminoacylpeptide hydrolase. Engineered: yes
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Source:
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Escherichia coli. Organism_taxid: 83333. Strain: k12. Gene: pepn, b0932, jw0915. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.57Å
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R-factor:
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0.114
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R-free:
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0.139
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Authors:
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G.Peng,V.Olieric,A.G.Mcewen,C.Schmitt,S.Albrecht,J.Cavarelli,C.Tarnus
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Key ref:
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G.Peng
et al.
(2017).
Insight into the remarkable affinity and selectivity of the aminobenzosuberone scaffold for the M1 aminopeptidases family based on structure analysis.
Proteins,
85,
1413-1421.
PubMed id:
DOI:
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Date:
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18-Nov-16
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Release date:
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19-Apr-17
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PROCHECK
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Headers
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References
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P04825
(AMPN_ECOLI) -
Aminopeptidase N from Escherichia coli (strain K12)
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Seq:
Struc:
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870 a.a.
868 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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Enzyme class:
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E.C.3.4.11.2
- membrane alanyl aminopeptidase.
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Reaction:
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Release of an N-terminal amino acid, Xaa-|-Xbb- from a peptide, amide or arylamide. Xaa is preferably Ala, but may be most amino acids including Pro (slow action). When a terminal hydrophobic residue is followed by a prolyl residue, the two may be released as an intact Xaa-Pro dipeptide.
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Cofactor:
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Zn(2+)
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DOI no:
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Proteins
85:1413-1421
(2017)
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PubMed id:
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Insight into the remarkable affinity and selectivity of the aminobenzosuberone scaffold for the M1 aminopeptidases family based on structure analysis.
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G.Peng,
A.G.McEwen,
V.Olieric,
C.Schmitt,
S.Albrecht,
J.Cavarelli,
C.Tarnus.
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ABSTRACT
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Aminopeptidases are ubiquitous hydrolases that cleave the N-terminal residues of
proteins and oligopeptides. They are broadly distributed throughout all kingdoms
of life and have been implicated in a wide variety of physiological processes,
including viral infection, parasite metabolism, protein processing, regulation
of peptide hormones, and cancer cell proliferation. Members of the M1 family,
also termed gluzincins, are defined by two highly conserved motifs in the
catalytic domain: a zinc-binding motif, HEXXH-(X18)-E; and an exopeptidase
motif, GXMEN. We report the high-resolution X-ray structures of E. coli
aminopeptidase N (PepN) in complex with three aminobenzosuberone scaffolds that
display various Ki values (50, 0.33, and 0.034 µM) and provide a compelling
view of the outstanding selectivity of these chemical entities for the M1
aminopeptidases. This series of inhibitors interacts as transition state mimics
with highly conserved residues of the catalytic machinery and substrate
recognition sites. Structural comparisons and model-building studies allowed a
deep interpretation of the SAR observed for bacterial, as well as mammalian
enzymes. Proteins 2017; 85:1413-1421. © 2017 Wiley Periodicals, Inc.
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