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PDBsum entry 4omc
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Hydrolase/hydrolase inhibitor
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PDB id
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4omc
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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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X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-phac-rvr-amba
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Structure:
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Furin. Chain: a, b, c, d, e, f. Fragment: unp residues 108-574. Synonym: dibasic-processing enzyme, paired basic amino acid residue- cleaving enzyme, pace. Engineered: yes. Meta-guanidinomethyl-phenylacetyl-arg-val-arg- (amidomethyl)benzamidine. Chain: h, i, j, k, l, n.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: fur, furin, pace, pcsk3. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell: hek293s. Synthetic: yes
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Resolution:
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2.30Å
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R-factor:
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0.185
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R-free:
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0.216
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Authors:
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S.O.Dahms,M.E.Than
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Key ref:
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S.O.Dahms
et al.
(2014).
X-ray structures of human furin in complex with competitive inhibitors.
Acs Chem Biol,
9,
1113-1118.
PubMed id:
DOI:
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Date:
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27-Jan-14
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Release date:
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09-Apr-14
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PROCHECK
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Headers
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References
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P09958
(FURIN_HUMAN) -
Furin from Homo sapiens
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Seq:
Struc:
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794 a.a.
466 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.3.4.21.75
- furin.
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Reaction:
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Release of mature proteins from their proproteins by cleavage of Arg- Xaa-Yaa-Arg-|-Zaa bonds, where Xaa can be any amino acid and Yaa is Arg or Lys. Releases albumin, complement component C3 and von Willebrand factor from their respective precursors.
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DOI no:
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Acs Chem Biol
9:1113-1118
(2014)
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PubMed id:
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X-ray structures of human furin in complex with competitive inhibitors.
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S.O.Dahms,
K.Hardes,
G.L.Becker,
T.Steinmetzer,
H.Brandstetter,
M.E.Than.
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ABSTRACT
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Furin inhibitors are promising therapeutics for the treatment of cancer and
numerous infections caused by bacteria and viruses, including the highly lethal
Bacillus anthracis or the pandemic influenza virus. Development and improvement
of inhibitors for pharmacological use require a detailed knowledge of the
protease's substrate and inhibitor binding properties. Here we present a novel
preparation of human furin and the first crystal structures of this enzyme in
complex with noncovalent inhibitors. We show the inhibitor exchange by soaking,
allowing the investigation of additional inhibitors and substrate analogues.
Thus, our work provides a basis for the rational design of furin inhibitors.
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Links
