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PDBsum entry 2rg3
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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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Covalent complex structure of elastase
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Structure:
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Leukocyte elastase. Chain: a. Synonym: elastase-2, neutrophil elastase, pmn elastase, bone marrow serine protease, medullasin, human leukocyte elastase, hle. Engineered: yes
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Source:
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Homo sapiens. Human. Gene: ela2. Expressed in: escherichia coli
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Resolution:
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Authors:
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W.Huang,Y.Yamamoto
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Key ref:
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W.Huang
et al.
(2008).
X-ray snapshot of the mechanism of inactivation of human neutrophil elastase by 1,2,5-thiadiazolidin-3-one 1,1-dioxide derivatives.
J Med Chem,
51,
2003-2008.
PubMed id:
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Date:
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02-Oct-07
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Release date:
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01-Jul-08
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PROCHECK
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Headers
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References
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P08246
(ELNE_HUMAN) -
Neutrophil elastase from Homo sapiens
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Seq:
Struc:
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267 a.a.
218 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.3.4.21.37
- leukocyte elastase.
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Reaction:
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Hydrolysis of proteins, including elastin. Preferential cleavage: Val-|-Xaa > Ala-|-Xaa.
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J Med Chem
51:2003-2008
(2008)
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PubMed id:
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X-ray snapshot of the mechanism of inactivation of human neutrophil elastase by 1,2,5-thiadiazolidin-3-one 1,1-dioxide derivatives.
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W.Huang,
Y.Yamamoto,
Y.Li,
D.Dou,
K.R.Alliston,
R.P.Hanzlik,
T.D.Williams,
W.C.Groutas.
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ABSTRACT
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The mechanism of action of a general class of mechanism-based inhibitors of
serine proteases, including human neutrophil elastase (HNE), has been elucidated
by determining the X-ray crystal structure of an enzyme-inhibitor complex. The
captured intermediate indicates that processing of inhibitor by the enzyme
generates an N-sulfonyl imine functionality that is tethered to Ser195, in
accordance with the postulated mechanism of action of this class of inhibitors.
The identity of the HNE-N-sulfonyl imine species was further corroborated using
electrospray ionization mass spectrometry.
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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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D.Dou,
G.He,
K.R.Alliston,
and
W.C.Groutas
(2011).
Dual function inhibitors of relevance to chronic obstructive pulmonary disease.
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Bioorg Med Chem Lett,
21,
3177-3180.
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E.Hajjar,
T.Broemstrup,
C.Kantari,
V.Witko-Sarsat,
and
N.Reuter
(2010).
Structures of human proteinase 3 and neutrophil elastase--so similar yet so different.
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FEBS J,
277,
2238-2254.
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Y.Li,
D.Dou,
G.He,
G.H.Lushington,
and
W.C.Groutas
(2009).
Mechanism-based inhibitors of serine proteases with high selectivity through optimization of S' subsite binding.
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Bioorg Med Chem,
17,
3536-3542.
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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.
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Links
