Crystal Structure of the Complex Between the Peptide Exosite Inhibitor E-76 and Coagulation Factor VIIA

Peptide exosite inhibitors of factor VIIa as anticoagulants.

GLC M 503 HAS WRONG CHIRALITY AT ATOM C1

IVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPS
TYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQ
QSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMR
SEPRPGVLLRAPFP

ISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLL
ADGVSCTPTVEYPCGKIPILE

PEG4000, t-butanol, sodium cacodylate, pH 5.5, VAPOR DIFFUSION, SITTING DROP, temperature 292K

Complex between soluble Tissue Factor and Factor VIIa

Complex of BPTI mutant, soluble Tissue Factor, and Factor VIIa

Peptide E-76 was synthesized on a solid support, then cleaved and purified

THE INHIBITOR IS BOUND TO THE ACTIVE SITE OF THE ENZYME.
THE UNBOUND FORM OF THE INHIBITOR IS D-PHE-PHE-ARG-CHLOROMETHYLKETONE.
UPON REACTION WITH PROTEIN IT FORMS TWO COVALENT BONDS:
1) A COVALENT BOND TO SER 195 FORMING A HEMIKETAL AR7 AND
2) A COVALENT BOND TO NE2 OF HIS 57

BULK SOLVENT MODEL WAS APPLIED

THERE IS UNPUBLISHED EXPERIMENTAL EVIDENCE THAT THE CARBOHYDRATE ATTACHED TO CHAINS L AND M DIFFERS FROM THAT DESCRIBED IN THIS ENTRY. SER 52 CARRIES 2 OR 3 GLUCOSE RESIDUES, AND SER 60 CARRIES ALPHA-L-FUCOSE. THE ELECTRON DENSITY IN THIS REGION IS IMPERFECT, AND WAS FIT WITHOUT THIS INFORMATION. THE FIT IS ONLY MODERATELY SUCCESFUL.

CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE PEPTIDE EXOSITE INHIBITOR E-76 AND COAGULATION FACTOR VIIA (E.C.3.4.21.21)

protein-peptide complex, HYDROLASE-HYDROLASE INHIBITOR COMPLEX