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'''The X-ray structure of the cis-3-chloroacrylic acid dehalogenase cis-CaaD inactivated with (R)-Oxirane-2-carboxylate''' | '''The X-ray structure of the cis-3-chloroacrylic acid dehalogenase cis-CaaD inactivated with (R)-Oxirane-2-carboxylate''' | ||
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[[Category: 4-oxalocrotonate tautomerase]] | [[Category: 4-oxalocrotonate tautomerase]] | ||
[[Category: 4ot family]] | [[Category: 4ot family]] | ||
[[Category: | [[Category: Covalent inhibitor]] | ||
[[Category: | [[Category: Hydratase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:02:46 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 04:02, 4 May 2008
The X-ray structure of the cis-3-chloroacrylic acid dehalogenase cis-CaaD inactivated with (R)-Oxirane-2-carboxylate
OverviewOverview
The bacterial degradation pathways for the nematocide 1,3-dichloropropene rely on hydrolytic dehalogenation reactions catalyzed by cis- and trans-3-chloroacrylic acid dehalogenases (cis-CaaD and CaaD, respectively). X-ray crystal structures of native cis-CaaD and cis-CaaD inactivated by (R)-oxirane-2-carboxylate were elucidated. They locate four known catalytic residues (Pro-1, Arg-70, Arg-73, and Glu-114) and two previously unknown, potential catalytic residues (His-28 and Tyr-103'). The Y103F and H28A mutants of these latter two residues displayed reductions in cis-CaaD activity confirming their importance in catalysis. The structure of the inactivated enzyme shows covalent modification of the Pro-1 nitrogen atom by (R)-2-hydroxypropanoate at the C3 position. The interactions in the complex implicate Arg-70 or a water molecule bound to Arg-70 as the proton donor for the epoxide ring-opening reaction and Arg-73 and His-28 as primary binding contacts for the carboxylate group. This proposed binding mode places the (R)-enantiomer, but not the (S)-enantiomer, in position to covalently modify Pro-1. The absence of His-28 (or an equivalent) in CaaD could account for the fact that CaaD is not inactivated by either enantiomer. The cis-CaaD structures support a mechanism in which Glu-114 and Tyr-103' activate a water molecule for addition to C3 of the substrate and His-28, Arg-70, and Arg-73 interact with the C1 carboxylate group to assist in substrate binding and polarization. Pro-1 provides a proton at C2. The involvement of His-28 and Tyr-103' distinguishes the cis-CaaD mechanism from the otherwise parallel CaaD mechanism. The two mechanisms probably evolved independently as the result of an early gene duplication of a common ancestor.
About this StructureAbout this Structure
2FLT is a Single protein structure of sequence from Coryneform bacterium. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of native and inactivated cis-3-chloroacrylic acid dehalogenase. Structural basis for substrate specificity and inactivation by (R)-oxirane-2-carboxylate., de Jong RM, Bazzacco P, Poelarends GJ, Johnson WH Jr, Kim YJ, Burks EA, Serrano H, Thunnissen AM, Whitman CP, Dijkstra BW, J Biol Chem. 2007 Jan 26;282(4):2440-9. Epub 2006 Nov 22. PMID:17121835 Page seeded by OCA on Sun May 4 04:02:46 2008