1cw2
CRYSTAL STRUCTURE OF THE COMPLEX OF BACTERIAL TRYPTOPHAN SYNTHASE WITH THE TRANSITION STATE ANALOGUE INHIBITOR 4-(2-HYDROXYPHENYLSULFINYL)-BUTYLPHOSPHONIC ACID
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OverviewOverview
In an effort to use a structure-based approach for the design of new, herbicides, the crystal structures of complexes of tryptophan synthase, with a series of phosphonate enzyme inhibitors were determined at 2.3 A or, higher resolution. These inhibitors were designed to mimic the transition, state formed during the alpha-reaction of the enzyme and, as expected, have affinities much greater than that of the natural substrate, indole-3-glycerol phosphate or its nonhydrolyzable analogue indole, propanol phosphate (IPP). These inhibitors are ortho-substituted, arylthioalkylphosphonate derivatives that have an sp(3)-hybridized sulfur, atom, designed to mimic the putative tetrahedral transition state at the, C3 atom of the indole, and lack the C2 atom to allow for higher, conformational flexibility. Overall, the inhibitors bind in a fashion, similar to that of IPP. Glu-49 and Phe-212 are the two active site, residues whose conformation changes upon inhibitor binding. A very short, hydrogen bond between a phosphonate oxygen and the Ser-235 hydroxyl oxygen, may be responsible for stabilization of the enzyme-inhibitor complexes., Implications for the mechanism of catalysis as well as directions for more, potent inhibitors are discussed.
About this StructureAbout this Structure
1CW2 is a Protein complex structure of sequences from Salmonella typhimurium with NA, PLP and HSP as ligands. Active as Tryptophan synthase, with EC number 4.2.1.20 Full crystallographic information is available from OCA.
ReferenceReference
Crystallographic studies of phosphonate-based alpha-reaction transition-state analogues complexed to tryptophan synthase., Sachpatzidis A, Dealwis C, Lubetsky JB, Liang PH, Anderson KS, Lolis E, Biochemistry. 1999 Sep 28;38(39):12665-74. PMID:10504236
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