Crystal Structure Analysis of the 1,2,3-tricarboxylate benzoic acid bound to sp-ASADH-2'5'-ADP complex

A cautionary tale of structure-guided inhibitor development against an essential enzyme in the aspartate-biosynthetic pathway.

double crystal monochromator and K-B pair of biomorph mirrors

ASA dehydrogenase, ASADH, Aspartate-beta-semialdehyde dehydrogenase

MGYTVAVVGATGAVGAQMIKMLEESTLPIDKIRYLASARSAGKSLKFKDQDITIEETTETAFEGVDIALFSAGSSTSAKY
APYAVKAGVVVVDNTSYFRQNPDVPLVVPEVNAHALDAHNGIIACPNCSTIQMMVALEPVRQKWGLDRIIVSTYQAVSGA
GMGAILETQRELREVLNDGVKPCDLHAEILPSGGDKKHYPIAFNALPQIDVFTDNDYTYEEMKMTKETKKIMEDDSIAVS
ATCVRIPVLSAHSESVYIETKEVAPIEEVKAAIAAFPGAVLEDDVAHQIYPQAINAVGSRDTFVGRIRKDLDAEKGIHMW
VVSDNLLKGAAWNSVQIAETLHERGLVRPTAELKFELKLEHHHHHH

15-22% PEG, 0.1 M Na acetate, 0.1 M MES (pH 6.5), 10 mM TCEP, 3% Ethylene glycol, VAPOR DIFFUSION, HANGING DROP, temperature 295K

1,2,3-tricarboxylate-benzoic acid sp-ASADH-NADP complex

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

Dehydrogenase, Nicotineamid-dinucleotide, OXIDOREDUCTASE

MGYTVAVVGATGAVGAQMIKMLEESTLPIDKIRYLASARSAGKSLKFKDQDITIEETTETAFEGVDIALFSAGSSTSAKY
APYAVKAGVVVVDNTSYFRQNPDVPLVVPEVNAHALDAHNGIIACPNCSTIQMMVALEPVRQKWGLDRIIVSTYQAVSGA
GMGAILETQRELREVLNDGVKPCDLHAEILPSGGDKKHYPIAFNALPQIDVFTDNDYTYEEMKMTKETKKIMEDDSIAVS
ATCVRIPVLSAHSESVYIETKEVAPIEEVKAAIAAFPGAVLEDDVAHQIYPQAINAVGSRDTFVGRIRKDLDAEKGIHMW
VVSDNLLKGAAWNSVQIAETLHERGLVRPTAELKFELK