CRYSTAL STRUCTURES OF ALPHA-LYTIC PROTEASE COMPLEXES WITH IRREVERSIBLY BOUND PHOSPHONATE ESTERS

Peptidic Phosphonylating Agents as Irreversible Inhibitors of Serine Proteases and Models of the Tetrahedral Intermediates

Refined Structure of Alpha-Lytic Protease at 1.7 Angstroms Resolution. Analysis of Hydrogen Bonding and Solvent Structure

Molecular Structure of the Alpha-Lytic Protease from Myxobacter 495 at 2.8 Angstroms Resolution

ANIVGGIEYSINNASLCSVGFSVTRGATKGFVTAGHCGTVNATARIGGAVVGTFAARVFPGNDRAWVSLTSAQTLLPRVA
NGSSFVTVRGSTEAAVGAAVCRSGRTTGYQCGTITAKNVTANYAEGAVRGLTQGNACMGRGDSGGSWITSAGQAQGVMSG
GNVQSNGNNCGIPASQRSSLFERLQPILSQYGLSLVTG

THE PVA RESIDUE IN THE INHIBITOR IS THE ALPHA-AMINO
PHOSPHONIC ACID ANALOG OF VAL IN WHICH THE C-TERMINAL
CARBOXYL GROUP (COOH) HAS BEEN REPLACED WITH A PHOSPHONIC
ACID GROUP (PO(OH)2).

IN THE INHIBITOR, DESIGNATED CHAIN I, ESTER
BONDS ARE FORMED FROM PHOSPHONATE PHOSPHOROUS OF THE OG
OF SER E 195 AND TO O1 OF THE LAC I -1.

INHIBITOR NUMBERING (CHAIN *I*, 5 TO -2) IS BY
ANALOGY TO PROTEASE SUBSTRATE NOMENCLATURE IN WHICH THE
RESIDUE PRIOR TO THE SCISSILE BOND IS THE *I* 1
RESIDUE, THE NEXT TOWARDS THE N-TERMINUS IS THE *I* 2 RESIDUE,
ETC. RESIDUES TOWARDS THE C-TERMINUS
ARE NUMBERED *I* -1 THEN *I* -2, ETC.
(I. SCHECTER, A. BERGER, BIOCHEM. BIOPHYS. RES. COMMUN. 27,
(1967) 157.

SERINE PROTEINASE, HYDROLASE-HYDROLASE INHIBITOR complex

MYVSNHRSRRVARVSVSCLVAALAAMSCGAALAADQVDPQLKFAMQRDLGIFPTQLPQYLQTEKLARTQAAAIEREFGAQ
FAGSWIERNEDGSFKLVAATSGARKSSTLGGVEVRNVRYSLKQLQSAMEQLDAGANARVKGVSKPLDGVQSWYVDPRSNA
VVVKVDDGATEAGVDFVALSGADSAQVRIESSPGKLQTTANIVGGIEYSINNASLCSVGFSVTRGATKGFVTAGHCGTVN
ATARIGGAVVGTFAARVFPGNDRAWVSLTSAQTLLPRVANGSSFVTVRGSTEAAVGAAVCRSGRTTGYQCGTITAKNVTA
NYAEGAVRGLTQGNACMGRGDSGGSWITSAGQAQGVMSGGNVQSNGNNCGIPASQRSSLFERLQPILSQYGLSLVTG

BINDING SITE FOR CHAIN I OF PHOSPHONATE ESTER INHIBITOR