1s0y
From Proteopedia
(New page: 200px<br /><applet load="1s0y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s0y, resolution 2.30Å" /> '''The structure of tra...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1s0y.gif|left|200px]]<br /><applet load="1s0y" size=" | + | [[Image:1s0y.gif|left|200px]]<br /><applet load="1s0y" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1s0y, resolution 2.30Å" /> | caption="1s0y, resolution 2.30Å" /> | ||
'''The structure of trans-3-chloroacrylic acid dehalogenase, covalently inactivated by the mechanism-based inhibitor 3-bromopropiolate at 2.3 Angstrom resolution'''<br /> | '''The structure of trans-3-chloroacrylic acid dehalogenase, covalently inactivated by the mechanism-based inhibitor 3-bromopropiolate at 2.3 Angstrom resolution'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Isomer-specific 3-chloroacrylic acid dehalogenases function in the | + | Isomer-specific 3-chloroacrylic acid dehalogenases function in the bacterial degradation of 1,3-dichloropropene, a compound used in agriculture to kill plant-parasitic nematodes. The crystal structure of the heterohexameric trans-3-chloroacrylic acid dehalogenase (CaaD) from Pseudomonas pavonaceae 170 inactivated by 3-bromopropiolate shows that Glu-52 in the alpha-subunit is positioned to function as the water-activating base for the addition of a hydroxyl group to C-3 of 3-chloroacrylate and 3-bromopropiolate, whereas the nearby Pro-1 in the beta-subunit is positioned to provide a proton to C-2. Two arginine residues, alphaArg-8 and alphaArg-11, interact with the C-1 carboxylate groups, thereby polarizing the alpha,beta-unsaturated acids. The reaction with 3-chloroacrylate results in the production of an unstable halohydrin, 3-chloro-3-hydroxypropanoate, which decomposes into the products malonate semialdehyde and HCl. In the inactivation mechanism, however, malonyl bromide is produced, which irreversibly alkylates the betaPro-1. CaaD is related to 4-oxalocrotonate tautomerase, with which it shares an N-terminal proline. However, in 4-oxalocrotonate tautomerase, Pro-1 functions as a base participating in proton transfer within a hydrophobic active site, whereas in CaaD, the acidic proline is stabilized in a hydrophilic active site. The altered active site environment of CaaD thus facilitates a previously unknown reaction in the tautomerase superfamily, the hydration of the alpha,beta-unsaturated bonds of trans-3-chloroacrylate and 3-bromopropiolate. The mechanism for these hydration reactions represents a novel catalytic strategy that results in carbon-halogen bond cleavage. |
==About this Structure== | ==About this Structure== | ||
| - | 1S0Y is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Pseudomonas_pavonaceae Pseudomonas pavonaceae] with MLA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1S0Y is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Pseudomonas_pavonaceae Pseudomonas pavonaceae] with <scene name='pdbligand=MLA:'>MLA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S0Y OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Pseudomonas pavonaceae]] | [[Category: Pseudomonas pavonaceae]] | ||
[[Category: Brugman, W.]] | [[Category: Brugman, W.]] | ||
| - | [[Category: Dijkstra, B | + | [[Category: Dijkstra, B W.]] |
| - | [[Category: Jong, R | + | [[Category: Jong, R M.de.]] |
| - | [[Category: Poelarends, G | + | [[Category: Poelarends, G J.]] |
| - | [[Category: Whitman, C | + | [[Category: Whitman, C P.]] |
[[Category: MLA]] | [[Category: MLA]] | ||
[[Category: covalent modification]] | [[Category: covalent modification]] | ||
| Line 27: | Line 27: | ||
[[Category: tautomerase family]] | [[Category: tautomerase family]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:56:46 2008'' |
Revision as of 12:56, 21 February 2008
|
The structure of trans-3-chloroacrylic acid dehalogenase, covalently inactivated by the mechanism-based inhibitor 3-bromopropiolate at 2.3 Angstrom resolution
Overview
Isomer-specific 3-chloroacrylic acid dehalogenases function in the bacterial degradation of 1,3-dichloropropene, a compound used in agriculture to kill plant-parasitic nematodes. The crystal structure of the heterohexameric trans-3-chloroacrylic acid dehalogenase (CaaD) from Pseudomonas pavonaceae 170 inactivated by 3-bromopropiolate shows that Glu-52 in the alpha-subunit is positioned to function as the water-activating base for the addition of a hydroxyl group to C-3 of 3-chloroacrylate and 3-bromopropiolate, whereas the nearby Pro-1 in the beta-subunit is positioned to provide a proton to C-2. Two arginine residues, alphaArg-8 and alphaArg-11, interact with the C-1 carboxylate groups, thereby polarizing the alpha,beta-unsaturated acids. The reaction with 3-chloroacrylate results in the production of an unstable halohydrin, 3-chloro-3-hydroxypropanoate, which decomposes into the products malonate semialdehyde and HCl. In the inactivation mechanism, however, malonyl bromide is produced, which irreversibly alkylates the betaPro-1. CaaD is related to 4-oxalocrotonate tautomerase, with which it shares an N-terminal proline. However, in 4-oxalocrotonate tautomerase, Pro-1 functions as a base participating in proton transfer within a hydrophobic active site, whereas in CaaD, the acidic proline is stabilized in a hydrophilic active site. The altered active site environment of CaaD thus facilitates a previously unknown reaction in the tautomerase superfamily, the hydration of the alpha,beta-unsaturated bonds of trans-3-chloroacrylate and 3-bromopropiolate. The mechanism for these hydration reactions represents a novel catalytic strategy that results in carbon-halogen bond cleavage.
About this Structure
1S0Y is a Protein complex structure of sequences from Pseudomonas pavonaceae with as ligand. Full crystallographic information is available from OCA.
Reference
The X-ray structure of trans-3-chloroacrylic acid dehalogenase reveals a novel hydration mechanism in the tautomerase superfamily., de Jong RM, Brugman W, Poelarends GJ, Whitman CP, Dijkstra BW, J Biol Chem. 2004 Mar 19;279(12):11546-52. Epub 2003 Dec 29. PMID:14701869
Page seeded by OCA on Thu Feb 21 14:56:46 2008
