2.0 ANGSTROM STRUCTURE OF INTACT ALPHA-1-ANTITRYPSIN: A CANONICAL TEMPLATE FOR ACTIVE SERPINS

Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease.

Wildtype Alpha1-Antitrypsin is in the Canonical Inhibitory Conformation

ALPHA-1-PROTEINASE INHIBITOR, ALPHA-1-ANTIPROTEINASE

MDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFAFSLYRQLAHQSNSTNIFFSPVSIATAFAMLSLGTKADTHDEILEGL
NFNLTEIPEAQIHEGFQELLRTLNQPDSQLQLTTGNGLFLSEGLKLVDKFLEDVKKLYHSEAFTVNFGDTEEAKKQINDY
VEKGTQGKIVDLVKELDRDTVFALVNYIFFKGKWERPFEVKDTEEEDFHVDQVTTVKVPMMKRLGMFNIQHCKKLSSWVL
LMKYLGNATAIFFLPDEGKLQHLENELTHDIITKFLENEDRRSASLHLPKLSITGTYDLKSVLGQLGITKVFSNGADLSG
VTEEAPLKLSKAVHKAVLTIDEKGTEAAGAMFLEAIPMSIPPEVKFNKPFVFLMIEQNTKSPLFMGKVVNPTQK

DATA WERE COLLECTED USING THE OSCILLATION METHOD.

24% PEG 4000, 0.2 M SODIUM ACETATE, 0.1M TRIS-HCL PH 6.0, 2MM FESO4.7H20

MODIFIED ALPHA-1-ANTITRYPSIN (TETRAGONAL FORM 1)

MODIFIED ALPHA-1-PROTEINASE INHIBITOR (HEXAGONAL)

MODIFIED ALPHA-1-ANTITRYPSIN (TETRAGONAL FORM 2)

INTACT RECOMBINED ALPHA-1-ANTITRYPSIN MUTANT PHE 51 TO LEU

INTACT WILDTYPE RECOMBINANT ALPHA-1-ANTITRYPSIN

THERMOSTABLE VARIANT ALPHA1-ANTITRYPSIN (PDB ENTRY 1PSI)

THE N-TERMINAL RESIDUES 1-22 WERE NOT OBSERVED IN THE ELECTRON DENSITY MAPS

SERINE PROTEASE INHIBITOR, SERPIN, GLYCOPROTEIN, POLYMORPHISM, EMPHYSEMA, DISEASE MUTATION, ACUTE PHASE