1ew8
From Proteopedia
(New page: 200px<br /><applet load="1ew8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ew8, resolution 2.2Å" /> '''ALKALINE PHOSPHATASE ...) |
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| - | [[Image:1ew8.gif|left|200px]]<br /><applet load="1ew8" size=" | + | [[Image:1ew8.gif|left|200px]]<br /><applet load="1ew8" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ew8, resolution 2.2Å" /> | caption="1ew8, resolution 2.2Å" /> | ||
'''ALKALINE PHOSPHATASE (E.C. 3.1.3.1) COMPLEX WITH PHOSPHONOACETIC ACID'''<br /> | '''ALKALINE PHOSPHATASE (E.C. 3.1.3.1) COMPLEX WITH PHOSPHONOACETIC ACID'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Two high resolution crystal structures of Escherichia coli alkaline | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1EW8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ZN, PO4, SO4, MG and PAE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alkaline_phosphatase Alkaline phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.1 3.1.3.1] Full crystallographic information is available from [http:// | + | 1EW8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=PAE:'>PAE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alkaline_phosphatase Alkaline phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.1 3.1.3.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EW8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Antonelli, S | + | [[Category: Antonelli, S M.]] |
| - | [[Category: Holtz, K | + | [[Category: Holtz, K M.]] |
| - | [[Category: Kantrowitz, E | + | [[Category: Kantrowitz, E R.]] |
| - | [[Category: Myers, J | + | [[Category: Myers, J K.]] |
[[Category: Stec, B.]] | [[Category: Stec, B.]] | ||
| - | [[Category: Widlanski, T | + | [[Category: Widlanski, T S.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: PAE]] | [[Category: PAE]] | ||
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[[Category: enzyme-inhibitor complex]] | [[Category: enzyme-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:32:07 2008'' |
Revision as of 10:32, 21 February 2008
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ALKALINE PHOSPHATASE (E.C. 3.1.3.1) COMPLEX WITH PHOSPHONOACETIC ACID
Overview
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.
About this Structure
1EW8 is a Single protein structure of sequence from Escherichia coli with , , , and as ligands. Active as Alkaline phosphatase, with EC number 3.1.3.1 Full crystallographic information is available from OCA.
Reference
Alternate modes of binding in two crystal structures of alkaline phosphatase-inhibitor complexes., Holtz KM, Stec B, Myers JK, Antonelli SM, Widlanski TS, Kantrowitz ER, Protein Sci. 2000 May;9(5):907-15. PMID:10850800
Page seeded by OCA on Thu Feb 21 12:32:07 2008
Categories: Alkaline phosphatase | Escherichia coli | Single protein | Antonelli, S M. | Holtz, K M. | Kantrowitz, E R. | Myers, J K. | Stec, B. | Widlanski, T S. | MG | PAE | PO4 | SO4 | ZN | Enzyme-inhibitor complex
