1px0: Difference between revisions
New page: left|200px<br /><applet load="1px0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1px0, resolution 1.90Å" /> '''Crystal structure of... |
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[[Image:1px0.jpg|left|200px]]<br /><applet load="1px0" size=" | [[Image:1px0.jpg|left|200px]]<br /><applet load="1px0" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1px0, resolution 1.90Å" /> | caption="1px0, resolution 1.90Å" /> | ||
'''Crystal structure of the haloalcohol dehalogenase HheC complexed with the haloalcohol mimic (R)-1-para-nitro-phenyl-2-azido-ethanol'''<br /> | '''Crystal structure of the haloalcohol dehalogenase HheC complexed with the haloalcohol mimic (R)-1-para-nitro-phenyl-2-azido-ethanol'''<br /> | ||
==Overview== | ==Overview== | ||
Haloalcohol dehalogenases are bacterial enzymes that catalyze the | Haloalcohol dehalogenases are bacterial enzymes that catalyze the cofactor-independent dehalogenation of vicinal haloalcohols such as the genotoxic environmental pollutant 1,3-dichloro-2-propanol, thereby producing an epoxide, a chloride ion and a proton. Here we present X-ray structures of the haloalcohol dehalogenase HheC from Agrobacterium radiobacter AD1, and complexes of the enzyme with an epoxide product and chloride ion, and with a bound haloalcohol substrate mimic. These structures support a catalytic mechanism in which Tyr145 of a Ser-Tyr-Arg catalytic triad deprotonates the haloalcohol hydroxyl function to generate an intramolecular nucleophile that substitutes the vicinal halogen. Haloalcohol dehalogenases are related to the widespread family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDR family), which use a similar Ser-Tyr-Lys/Arg catalytic triad to catalyze reductive or oxidative conversions of various secondary alcohols and ketones. Our results reveal the first structural details of an SDR-related enzyme that catalyzes a substitutive dehalogenation reaction rather than a redox reaction, in which a halide-binding site is found at the location of the NAD(P)H binding site. Structure-based sequence analysis reveals that the various haloalcohol dehalogenases have likely originated from at least two different NAD-binding SDR precursors. | ||
==About this Structure== | ==About this Structure== | ||
1PX0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Agrobacterium_tumefaciens Agrobacterium tumefaciens] with RPN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1PX0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Agrobacterium_tumefaciens Agrobacterium tumefaciens] with <scene name='pdbligand=RPN:'>RPN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PX0 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Agrobacterium tumefaciens]] | [[Category: Agrobacterium tumefaciens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Dijkstra, B | [[Category: Dijkstra, B W.]] | ||
[[Category: Janssen, D | [[Category: Janssen, D B.]] | ||
[[Category: Jong, R | [[Category: Jong, R M.de.]] | ||
[[Category: Kalk, K | [[Category: Kalk, K H.]] | ||
[[Category: Rozeboom, H | [[Category: Rozeboom, H J.]] | ||
[[Category: Tang, L.]] | [[Category: Tang, L.]] | ||
[[Category: Tiesinga, J | [[Category: Tiesinga, J J.W.]] | ||
[[Category: RPN]] | [[Category: RPN]] | ||
[[Category: haloalcohol dehalogenase]] | [[Category: haloalcohol dehalogenase]] | ||
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[[Category: short-chain dehydrogenase/reductase]] | [[Category: short-chain dehydrogenase/reductase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:33:26 2008'' | ||
Revision as of 12:33, 21 February 2008
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Crystal structure of the haloalcohol dehalogenase HheC complexed with the haloalcohol mimic (R)-1-para-nitro-phenyl-2-azido-ethanol
Overview
Haloalcohol dehalogenases are bacterial enzymes that catalyze the cofactor-independent dehalogenation of vicinal haloalcohols such as the genotoxic environmental pollutant 1,3-dichloro-2-propanol, thereby producing an epoxide, a chloride ion and a proton. Here we present X-ray structures of the haloalcohol dehalogenase HheC from Agrobacterium radiobacter AD1, and complexes of the enzyme with an epoxide product and chloride ion, and with a bound haloalcohol substrate mimic. These structures support a catalytic mechanism in which Tyr145 of a Ser-Tyr-Arg catalytic triad deprotonates the haloalcohol hydroxyl function to generate an intramolecular nucleophile that substitutes the vicinal halogen. Haloalcohol dehalogenases are related to the widespread family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDR family), which use a similar Ser-Tyr-Lys/Arg catalytic triad to catalyze reductive or oxidative conversions of various secondary alcohols and ketones. Our results reveal the first structural details of an SDR-related enzyme that catalyzes a substitutive dehalogenation reaction rather than a redox reaction, in which a halide-binding site is found at the location of the NAD(P)H binding site. Structure-based sequence analysis reveals that the various haloalcohol dehalogenases have likely originated from at least two different NAD-binding SDR precursors.
About this Structure
1PX0 is a Single protein structure of sequence from Agrobacterium tumefaciens with RPN as ligand. Full crystallographic information is available from OCA.
Reference
Structure and mechanism of a bacterial haloalcohol dehalogenase: a new variation of the short-chain dehydrogenase/reductase fold without an NAD(P)H binding site., de Jong RM, Tiesinga JJ, Rozeboom HJ, Kalk KH, Tang L, Janssen DB, Dijkstra BW, EMBO J. 2003 Oct 1;22(19):4933-44. PMID:14517233
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