1C9D
CRYSTAL STRUCTURE OF THE COMPLEX OF BACTERIAL TRYPTOPHAN SYNTHASE WITH THE TRANSITION STATE ANALOGUE INHIBITOR 4-(2-HYDROXY-4-FLUOROPHENYLTHIO)-BUTYLPHOSPHONIC ACID
Summary for 1C9D
| Entry DOI | 10.2210/pdb1c9d/pdb |
| Related | 1C29 1C8V |
| Descriptor | TRYPTOPHAN SYNTHASE (ALPHA CHAIN), TRYPTOPHAN SYNTHASE (BETA CHAIN), 4-(2-HYDROXY-4-FLUOROPHENYLTHIO)-BUTYLPHOSPHONIC ACID, ... (6 entities in total) |
| Functional Keywords | 8-fold alpha-beta barrel, enzyme-inhibitor complex, lyase |
| Biological source | Salmonella typhimurium More |
| Total number of polymer chains | 2 |
| Total formula weight | 72236.16 |
| Authors | Lolis, E.,Sachpatzidis, A. (deposition date: 1999-08-02, release date: 1999-12-29, Last modification date: 2024-03-13) |
| Primary citation | Sachpatzidis, A.,Dealwis, C.,Lubetsky, J.B.,Liang, P.H.,Anderson, K.S.,Lolis, E. Crystallographic studies of phosphonate-based alpha-reaction transition-state analogues complexed to tryptophan synthase. Biochemistry, 38:12665-12674, 1999 Cited by PubMed Abstract: 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. PubMed: 10504236DOI: 10.1021/bi9907734 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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