2Z7F

Crystal structure of the complex of human neutrophil elastase with 1/2SLPI

Summary for 2Z7F

• Entry DOI: 10.2210/pdb2z7f/pdb
• Descriptor: Leukocyte elastase, Antileukoproteinase, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: serine protease, serine protease inhibitor, disease mutation, glycoprotein, hydrolase, zymogen, secreted, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P03973
• Total number of polymer chains: 2
• Total formula weight: 29576.42

Authors

Takimoto-Kamimura, M.,Fukushima, K. (deposition date: 2007-08-20, release date: 2008-08-26, Last modification date: 2024-10-30)

Primary citation

Koizumi, M.,Fujino, A.,Fukushima, K.,Kamimura, T.,Takimoto-Kamimura, M.
Complex of human neutrophil elastase with 1/2SLPI
J.SYNCHROTRON RADIAT., 15:308-311, 2008

PubMed Abstract: 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.

PubMed: 18421166
DOI: 10.1107/S0909049507060670

Experimental method

X-RAY DIFFRACTION (1.7 Å)