1HNE

Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-angstroms resolution

Summary for 1HNE

• Entry DOI: 10.2210/pdb1hne/pdb
• Related PRD ID: PRD_000402
• Descriptor: HUMAN LEUCOCYTE ELASTASE, METHOXYSUCCINYL-ALA-ALA-PRO-ALA CHLOROMETHYL KETONE INHIBITOR (3 entities in total)
• Functional Keywords: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 23796.92

Authors

Navia, M.A.,Mckeever, B.M.,Springer, J.P.,Lin, T.-Y.,Williams, H.R.,Fluder, E.M.,Dorn, C.P.,Hoogsteen, K. (deposition date: 1989-04-10, release date: 1989-10-15, Last modification date: 2024-10-16)

Primary citation

Navia, M.A.,McKeever, B.M.,Springer, J.P.,Lin, T.Y.,Williams, H.R.,Fluder, E.M.,Dorn, C.P.,Hoogsteen, K.
Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution.
Proc.Natl.Acad.Sci.USA, 86:7-11, 1989

PubMed Abstract: Human neutrophil elastase (HNE) has been implicated as a major contributor to tissue destruction in various disease states, including emphysema. The structure of HNE, at neutral pH, in complex with methoxysuccinyl-Ala-Ala-Pro-Ala chloromethyl ketone (MSACK), has been solved and refined to an R factor of 16.4% at 1.84-A resolution. Results are consistent with the currently accepted mechanism of peptide chloromethyl ketone inhibition of serine proteases, in that MSACK cross-links the catalytic residues His-57 and Ser-195. The structure of the HNE-MSACK complex is compared with that of porcine pancreatic elastase in complex with L-647,957, a beta-lactam inhibitor of both elastases. The distribution of positively charged residues on HNE is highly asymmetric and may play a role in its specific association with the underlying negatively charged proteoglycan matrix of the neutrophil granules in which the enzyme is stored.

PubMed: 2911584
DOI: 10.1073/pnas.86.1.7

Experimental method

X-RAY DIFFRACTION (1.84 Å)