The mode of action and the structure of a herbicide in complex with its target: binding of activated hydantocidin to the feedback regulation site of adenylosuccinate synthetase.

Fonné‐Pfister, Raymonde; Chemla, Philippe; Ward, Eric; Girardet, M.; Kreuz, Klaus; Honzatko, Richard B.; Fromm, Herbert J.; Schär, Hans‐Peter; Grütter, Markus G.; Cowan‐Jacob, Sandra W.

doi:10.1073/pnas.93.18.9431

Cited by 77 publications

(37 citation statements)

References 42 publications

(38 reference statements)

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“…The structure was solved by molecular replacement with the program AmoRe (27). The initial model was the E. coli synthetase (Protein Data Bank identifier 1SON) (18). Model building and refinement employed the programs XTALVIEW (28) and CNS (29), respectively.…”

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confidence: 99%

Recombinant Mouse Muscle Adenylosuccinate Synthetase

Iancu¹,

Borza²,

Choe

et al. 2001

Journal of Biological Chemistry

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Vertebrates possess two isozymes of adenylosuccinate synthetase. The acidic isozyme is similar to the synthetase from bacteria and plants, being involved in the de novo biosynthesis of AMP, whereas the basic isozyme participates in the purine nucleotide cycle. Reported here is the first instance of overexpression and crystal structure determination of a basic isozyme of adenylosuccinate synthetase. The recombinant mouse muscle enzyme purified to homogeneity in milligram quantities exhibits a specific activity comparable with that of the rat muscle enzyme isolated from tissue and K m parameters for GTP, IMP, and L-aspartate (12, 45, and 140 M, respectively) similar to those of the enzyme from Escherichia coli. The mouse muscle and E. coli enzymes have similar polypeptide folds, differing primarily in the conformation of loops, involved in substrate recognition and stabilization of the transition state. Residues 65-68 of the muscle isozyme adopt a conformation not observed in any previous synthetase structure. In its new conformation, segment 65-68 forms intramolecular hydrogen bonds with residues essential for the recognition of IMP and, in fact, sterically excludes IMP from the active site. Observed differences in ligand recognition among adenylosuccinate synthetases may be due in part to conformational variations in the IMP pocket of the ligand-free enzymes.

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confidence: 99%

Recombinant Mouse Muscle Adenylosuccinate Synthetase

Iancu¹,

Borza²,

Choe

et al. 2001

Journal of Biological Chemistry

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“…Hydantocidin was shown to be a proherbicide that, after phosphorylation at the 5' position, inhibits adenylosuccinate synthase (Fonné-Pfister et al, 1996). The mode of binding of hydantocidin 5'-monophosphate (HMP) to the target enzyme from E. coli was analyzed by determining the crystal structure of the enzyme inhibitor complex.…”

Section: Research For Finding New Target Sitesmentioning

confidence: 99%

Molecular Mechanism of Action of Herbicides

Jablonkai¹

2011

Herbicides - Mechanisms and Mode of Action

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“…Hydantocidin, known as pro-herbicide, is first converted into hydantocidin monophosphate (HMP), and this molecule mimics either IMP or AMP. Evidence from crystallographic studies of the enzyme showed that hydantocidin replaced IMP in the active site [7][8][9][10] . Hadacidin is also a natural substrate of AdSS, which was reported as a competitive inhibitor of aspartic acid but affecting the enzyme at a different site 11 .…”

Section: Adenylosuccinate Synthasementioning

confidence: 99%