1EW9: ALKALINE PHOSPHATASE (E.C. 3.1.3.1) COMPLEX WITH MERCAPTOMETHYL PHOSPHONATE

Citation:
Abstract
Two high resolution crystal structures of Escherichia coli alkaline phosphatase (AP) in the presence of phosphonate inhibitors are reported. The phosphonate compounds, phosphonoacetic acid (PAA) and mercaptomethylphosphonic acid (MMP), bind competitively to AP with dissociation constants of 5.5 and 0.6 mM, respectively. The structures of the complexes of AP with PAA and MMP were refined at high resolution to crystallographic R-values of 19.0 and 17.5%, respectively. Refinement of the AP-inhibitor complexes was carried out using X-PLOR. The final round of refinement was done using SHELXL-97. Crystallographic analyses of the inhibitor complexes reveal different binding modes for the two phosphonate compounds. The significant difference in binding constants can be attributed to these alternative binding modes observed in the high resolution X-ray structures. The phosphinyl group of PAA coordinates to the active site zinc ions in a manner similar to the competitive inhibitor and product inorganic phosphate. In contrast, MMP binds with its phosphonate moiety directed toward solvent. Both enzyme-inhibitor complexes exhibit close contacts, one of which has the chemical and geometrical potential to be considered an unconventional hydrogen bond of the type C-H...X.
PDB ID: 1EW9Download
MMDB ID: 19151
PDB Deposition Date: 2000/4/24
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 1EW9: dimeric; determined by author and by software (PISA,PQS)
Molecular Components in 1EW9
Label Count Molecule
Proteins (2 molecules)
2
Alkaline Phosphatase(Gene symbol: phoA)
Molecule annotation
Chemicals (12 molecules)
1
6
2
2
3
2
4
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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