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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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References listed in PDB file
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Key reference
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Title
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Complex of human neutrophil elastase with 1/2slpi.
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Authors
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M.Koizumi,
A.Fujino,
K.Fukushima,
T.Kamimura,
M.Takimoto-Kamimura.
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Ref.
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J Synchrotron Radiat, 2008,
15,
308-311.
[DOI no: ]
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PubMed id
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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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