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PDBsum entry 2z7f
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Hydrolase/hydrolase inhibitor
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PDB id
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2z7f
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Contents |
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* Residue conservation analysis
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Enzyme class:
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Chain E:
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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DOI no:
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J Synchrotron Radiat
15:308-311
(2008)
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PubMed id:
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Complex of human neutrophil elastase with 1/2SLPI.
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M.Koizumi,
A.Fujino,
K.Fukushima,
T.Kamimura,
M.Takimoto-Kamimura.
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ABSTRACT
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SLPI (secretory leukocyte protease inhibitor) is a 107-residue non-glycosylated
protease inhibitor, which inhibits a wide range of serine proteases, trypsin,
chymotrypsin, neutrophil elastase, chymase and cathepsin G. X-ray
crystallographic analyses have shown that SLPI comprises two separate domains of
similar architecture [Grütter, Fendrich, Huber & Bode (1988), EMBO J. 7,
345-351] and the C-terminal domain interacts with bovine alpha-chymotrypsin. In
order to understand SLPI's multiple functions against various serine proteases,
the complex HNE (human neutrophil elastase) has been co-crystallized with
1/2SLPI (recombinant C-terminal domain of SLPI; Arg58-Ala107), which has a
biological activity similar to full SLPI. The 1/2SLPI and HNE complex structure
was solved at 1.7 A resolution, and compared with the interaction mechanism of
elafin, which is a specific inhibitor of elastase. It was found that P1 Leu72i
and six hydrogen bonds between the main chains in the primary contact region
have sufficient ability to inhibit HNE and PPE (porcine pancreatic elastase),
and P5 Tyr68i is important in increasing the selectivity of 1/2SLPI against HNE.
The mechanisms of the functions of SLPI are relatively unknown, but the current
study could help understand the selectivity of SLPI against HNE and PPE.
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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.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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J.R.Banigan,
K.Mandal,
M.R.Sawaya,
V.Thammavongsa,
A.P.Hendrickx,
O.Schneewind,
T.O.Yeates,
and
S.B.Kent
(2010).
Determination of the X-ray structure of the snake venom protein omwaprin by total chemical synthesis and racemic protein crystallography.
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Protein Sci,
19,
1840-1849.
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PDB code:
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M.L.Zani,
K.Baranger,
N.Guyot,
S.Dallet-Choisy,
and
T.Moreau
(2009).
Protease inhibitors derived from elafin and SLPI and engineered to have enhanced specificity towards neutrophil serine proteases.
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Protein Sci,
18,
579-594.
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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
