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PDBsum entry 2djg
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114 a.a.
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161 a.a.
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68 a.a.
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Re-determination of the native structure of human dipeptidyl peptidase i (cathepsin c)
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Structure:
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Dipeptidyl-peptidase 1. Chain: a. Fragment: dipeptidyl-peptidase 1 exclusion domain chain. Synonym: cathepsin c. Engineered: yes. Dipeptidyl-peptidase 1. Chain: b. Fragment: dipeptidyl-peptidase 1 heavy chain. Synonym: cathepsin c.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ctsc. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell: bti-tn-5b1-4.
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Biol. unit:
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Dodecamer (from PDB file)
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Resolution:
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2.05Å
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R-factor:
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0.176
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R-free:
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0.221
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Authors:
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A.Molgaard,J.Arnau,C.Lauritzen,S.Larsen,G.Petersen,J.Pedersen
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Key ref:
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A.Mølgaard
et al.
(2007).
The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2.
Biochem J,
401,
645-650.
PubMed id:
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Date:
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02-Apr-06
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Release date:
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14-Nov-06
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PROCHECK
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Headers
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References
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P53634
(CATC_HUMAN) -
Dipeptidyl peptidase 1 from Homo sapiens
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Seq:
Struc:
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463 a.a.
114 a.a.
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Enzyme class:
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Chains A, B, C:
E.C.3.4.14.1
- dipeptidyl-peptidase I.
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Reaction:
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Release of an N-terminal dipeptide, Xaa-Xbb-|-Xcc, except when Xaa is Arg or Lys, or Xbb or Xcc is Pro.
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Biochem J
401:645-650
(2007)
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PubMed id:
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The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2.
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A.Mølgaard,
J.Arnau,
C.Lauritzen,
S.Larsen,
G.Petersen,
J.Pedersen.
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ABSTRACT
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hDDPI (human dipeptidyl peptidase I) is a lysosomal cysteine protease involved
in zymogen activation of granule-associated proteases, including granzymes A and
B from cytotoxic T-lymphocytes and natural killer cells, cathepsin G and
neutrophil elastase, and mast cell tryptase and chymase. In the present paper,
we provide the first crystal structure of an hDPPI-inhibitor complex. The
inhibitor Gly-Phe-CHN2 (Gly-Phe-diazomethane) was co-crystallized with hDPPI and
the structure was determined at 2.0 A (1 A=0.1 nm) resolution. The structure of
the native enzyme was also determined to 2.05 A resolution to resolve apparent
discrepancies between the complex structure and the previously published
structure of the native enzyme. The new structure of the native enzyme is,
within the experimental error, identical with the structure of the
enzyme-inhibitor complex presented here. The inhibitor interacts with three
subunits of hDPPI, and is covalently bound to Cys234 at the active site. The
interaction between the totally conserved Asp1 of hDPPI and the ammonium group
of the inhibitor forms an essential interaction that mimics enzyme-substrate
interactions. The structure of the inhibitor complex provides an explanation of
the substrate specificity of hDPPI, and gives a background for the design of new
inhibitors.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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E.Deu,
M.J.Leyva,
V.E.Albrow,
M.J.Rice,
J.A.Ellman,
and
M.Bogyo
(2010).
Functional studies of Plasmodium falciparum dipeptidyl aminopeptidase I using small molecule inhibitors and active site probes.
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Chem Biol,
17,
808-819.
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M.Renko,
U.Požgan,
D.Majera,
and
D.Turk
(2010).
Stefin A displaces the occluding loop of cathepsin B only by as much as required to bind to the active site cleft.
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FEBS J,
277,
4338-4345.
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PDB code:
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M.Kurban,
M.Wajid,
Y.Shimomura,
R.Bahhady,
A.G.Kibbi,
and
A.M.Christiano
(2009).
Evidence for a founder mutation in the cathepsin C gene in three families with Papillon-Lefèvre syndrome.
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Dermatology,
219,
289-294.
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S.Hyun,
A.Han,
and
J.Yu
(2009).
Photocrosslinking of RNA and photomet-containing amphiphilic alpha-helical peptides.
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Chembiochem,
10,
987-989.
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G.Hamilton,
J.D.Colbert,
A.W.Schuettelkopf,
and
C.Watts
(2008).
Cystatin F is a cathepsin C-directed protease inhibitor regulated by proteolysis.
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EMBO J,
27,
499-508.
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I.Redzynia,
A.Ljunggren,
M.Abrahamson,
J.S.Mort,
J.C.Krupa,
M.Jaskolski,
and
G.Bujacz
(2008).
Displacement of the occluding loop by the parasite protein, chagasin, results in efficient inhibition of human cathepsin B.
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J Biol Chem,
283,
22815-22825.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
