RECRUITING ZINC TO MEDIATE POTENT, SPECIFIC INHIBITION OF SERINE PROTEASES

Design of potent selective zinc-mediated serine protease inhibitors.

COMPLEXED WITH (5-AMIDINO-2-BENZIMIDAZOLYL)(2-BENZIMIDAZOLYL)METHANE

IVGGYTCGANTVPYQVSLNSGYHFCGGSLINSQWVVSAAHCYKSGIQVRLGEDNINVVEGNEQFISASKSIVHPSYNSNT
LNNDIMLIKLKSAASLNSRVASISLPTSCASAGTQCLISGWGNTKSSGTSYPDVLKCLKAPILSDSSCKSAYPGQITSNM
FCAGYLEGGKDSCQGDSGGPVVCSGKLQGIVSWGSGCAQKNKPGVYTKVCNYVSWIKQTIASN

TRYPSIN-BENZAMIDINE, P3(1) 2 1 WERE GROWN BY VAPOR DIFFUSION, AS DESCRIBED FOR P2(1) 2(1) 2(1) (LARGE CELL) (MANGEL, ET AL., BIOCHEMISTRY 29, 8351-8357, 1990) THE CRYSTAL WAS SOAKED IN A SOLUTION OF 0.10 M TRIS, 2.02 M MGSO4 . 7 H2O, PH 8.21, 2.0 % DMSO, SATURATED IN HEMI-BABIM OVER A PERIOD OF SEVERAL DAYS WITH SEVERAL REPLACEMENTS OF THE SOAKING SOLUTION.

HIS40 AND HIS91 ARE MONOPROTONATED ON THE EPSILON NITROGEN. HIS57 IS MONOPROTONATED ON THE DELTA NITROGEN.

BULK SOLVENT TERMS INCLUDED IN FOB FILE CREATED WITH STANDARD X-PLOR SCRIPT.

ZN(II)-MEDIATED SERINE PROTEASE INHIBITORS, PH DEPENDENCE, ZN(II) AFFINITY STUCTURE-BASED DRUG DESIGN, SERINE PROTEASE SERINE PROTEASE/INHIBITOR, HYDROLASE-HYDROLASE INHIBITOR COMPLEX