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PDBsum entry 3bc3
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Contents |
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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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Exploring inhibitor binding at the s subsites of cathepsin l
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Structure:
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Cathepsin l heavy and light chains. Chain: a, b. Fragment: unp residues 114-333. Synonym: (ec 3.4.22.15) (major excreted protein) (mep). Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ctsl. Expressed in: pichia pastoris. Expression_system_taxid: 4922
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Resolution:
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2.20Å
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R-factor:
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0.183
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R-free:
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0.234
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Authors:
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S.F.Chowdhury,L.Joseph,S.Kumar,S.R.Tulsidas,S.Bhat,E.Ziomek,R.M.Nard, J.Sivaraman,E.O.Purisima
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Key ref:
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S.F.Chowdhury
et al.
(2008).
Exploring inhibitor binding at the S' subsites of cathepsin L.
J Med Chem,
51,
1361-1368.
PubMed id:
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Date:
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12-Nov-07
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Release date:
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18-Mar-08
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PROCHECK
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Headers
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References
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P07711
(CATL1_HUMAN) -
Procathepsin L from Homo sapiens
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Seq:
Struc:
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333 a.a.
215 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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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.3.4.22.15
- cathepsin L.
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Reaction:
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Specificity close to that of papain. As compared to cathepsin B, cathepsin L exhibits higher activity towards protein substrates, but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-dipeptidase activity.
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J Med Chem
51:1361-1368
(2008)
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PubMed id:
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Exploring inhibitor binding at the S' subsites of cathepsin L.
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S.F.Chowdhury,
L.Joseph,
S.Kumar,
S.R.Tulsidas,
S.Bhat,
E.Ziomek,
R.Ménard,
J.Sivaraman,
E.O.Purisima.
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ABSTRACT
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We report a series of noncovalent, reversible inhibitors of cathepsin L that
have been designed to explore additional binding interactions with the S'
subsites. The design was based on our previously reported crystal structure that
suggested the possibility of engineering increased interactions with the S'
subsites ( Chowdhury et al. J. Med. Chem. 2002, 45, 5321-5329 ). A
representative of these new inhibitors has been co-crystallized with mature
cathepsin L, and the structure has been solved and refined at 2.2 A. The
inhibitors described in this work extend farther into the S' subsites of
cathepsins than any inhibitors reported in the literature thus far. These
interactions appear to make use of a S3' subsite that can potentially be
exploited for enhanced specificity and/or affinity.
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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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M.A.Adams-Cioaba,
J.C.Krupa,
C.Xu,
J.S.Mort,
and
J.Min
(2011).
Structural basis for the recognition and cleavage of histone H3 by cathepsin L.
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Nat Commun,
2,
197.
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PDB codes:
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L.P.Coppini,
N.M.Barros,
M.Oliveira,
I.Y.Hirata,
M.F.Alves,
T.Paschoalin,
D.M.Assis,
M.A.Juliano,
L.Puzer,
D.Brömme,
and
A.K.Carmona
(2010).
Plasminogen hydrolysis by cathepsin S and identification of derived peptides as selective substrate for cathepsin V and cathepsin L inhibitor.
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Biol Chem,
391,
561-570.
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E.T.Larson,
F.Parussini,
M.H.Huynh,
J.D.Giebel,
A.M.Kelley,
L.Zhang,
M.Bogyo,
E.A.Merritt,
and
V.B.Carruthers
(2009).
Toxoplasma gondii cathepsin L is the primary target of the invasion-inhibitory compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl.
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J Biol Chem,
284,
26839-26850.
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PDB code:
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R.L.Cunha,
I.E.Gouvêa,
G.P.Feitosa,
M.F.Alves,
D.Brömme,
J.V.Comasseto,
I.L.Tersariol,
and
L.Juliano
(2009).
Irreversible inhibition of human cathepsins B, L, S and K by hypervalent tellurium compounds.
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Biol Chem,
390,
1205-1212.
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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
codes are
shown on the right.
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Links
