1uc4

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(New page: 200px<br /><applet load="1uc4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1uc4, resolution 1.80&Aring;" /> '''Structure of diol de...)
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caption="1uc4, resolution 1.80&Aring;" />
'''Structure of diol dehydratase complexed with (S)-1,2-propanediol'''<br />
'''Structure of diol dehydratase complexed with (S)-1,2-propanediol'''<br />
==Overview==
==Overview==
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Adenosylcobalamin-dependent diol dehydratase of Klebsiella oxytoca is, apparently not stereospecific and catalyzes the conversion of both (R)-, and (S)-1,2-propanediol to propionaldehyde. To explain this unusual, property of the enzyme, we analyzed the crystal structures of diol, dehydratase in complexes with cyanocobalamin and (R)- or, (S)-1,2-propanediol. (R)- and (S)-isomers are bound in a symmetrical, manner, although the hydrogen-bonding interactions between the substrate, and the active-site residues are the same. From the position of the, adenosyl radical in the modeled "distal" conformation, it is reasonable, for the radical to abstract the pro-R and pro-S hydrogens from (R)- and, (S)-isomers, respectively. The hydroxyl groups in the substrate radicals, would migrates from C(2) to C(1) by a suprafacial shift, resulting in the, stereochemical inversion at C(1). This causes 60 degrees clockwise and 70, degrees counterclockwise rotations of the C(1)-C(2) bond of the (R)- and, (S)-isomers, respectively, if viewed from K+. A modeling study of, 1,1-gem-diol intermediates indicated that new radical center C(2) becomes, close to the methyl group of 5'-deoxyadenosine. Thus, the hydrogen, back-abstraction (recombination) from 5'-deoxyadenosine by the product, radical is structurally feasible. It was also predictable that the, substitution of the migrating hydroxyl group by a hydrogen atom from, 5'-deoxyadenosine takes place with the inversion of the configuration at, C(2) of the substrate. Stereospecific dehydration of the 1,1-gem-diol, intermediates can also be rationalized by assuming that Asp-alpha335 and, Glu-alpha170 function as base catalysts in the dehydration of the (R)- and, (S)-isomers, respectively. The structure-based mechanism and, stereochemical courses of the reaction are proposed.
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Adenosylcobalamin-dependent diol dehydratase of Klebsiella oxytoca is apparently not stereospecific and catalyzes the conversion of both (R)- and (S)-1,2-propanediol to propionaldehyde. To explain this unusual property of the enzyme, we analyzed the crystal structures of diol dehydratase in complexes with cyanocobalamin and (R)- or (S)-1,2-propanediol. (R)- and (S)-isomers are bound in a symmetrical manner, although the hydrogen-bonding interactions between the substrate and the active-site residues are the same. From the position of the adenosyl radical in the modeled "distal" conformation, it is reasonable for the radical to abstract the pro-R and pro-S hydrogens from (R)- and (S)-isomers, respectively. The hydroxyl groups in the substrate radicals would migrates from C(2) to C(1) by a suprafacial shift, resulting in the stereochemical inversion at C(1). This causes 60 degrees clockwise and 70 degrees counterclockwise rotations of the C(1)-C(2) bond of the (R)- and (S)-isomers, respectively, if viewed from K+. A modeling study of 1,1-gem-diol intermediates indicated that new radical center C(2) becomes close to the methyl group of 5'-deoxyadenosine. Thus, the hydrogen back-abstraction (recombination) from 5'-deoxyadenosine by the product radical is structurally feasible. It was also predictable that the substitution of the migrating hydroxyl group by a hydrogen atom from 5'-deoxyadenosine takes place with the inversion of the configuration at C(2) of the substrate. Stereospecific dehydration of the 1,1-gem-diol intermediates can also be rationalized by assuming that Asp-alpha335 and Glu-alpha170 function as base catalysts in the dehydration of the (R)- and (S)-isomers, respectively. The structure-based mechanism and stereochemical courses of the reaction are proposed.
==About this Structure==
==About this Structure==
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1UC4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Klebsiella_oxytoca Klebsiella oxytoca] with NH4, K, CNC and PGO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Propanediol_dehydratase Propanediol dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.28 4.2.1.28] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UC4 OCA].
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1UC4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Klebsiella_oxytoca Klebsiella oxytoca] with <scene name='pdbligand=NH4:'>NH4</scene>, <scene name='pdbligand=K:'>K</scene>, <scene name='pdbligand=CNC:'>CNC</scene> and <scene name='pdbligand=PGO:'>PGO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Propanediol_dehydratase Propanediol dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.28 4.2.1.28] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UC4 OCA].
==Reference==
==Reference==
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[[Category: alpha/beta barrel]]
[[Category: alpha/beta barrel]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 03:43:35 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:22:51 2008''

Revision as of 13:22, 21 February 2008

Image:1uc4.jpg

1uc4, resolution 1.80Å

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Structure of diol dehydratase complexed with (S)-1,2-propanediol

Overview

Adenosylcobalamin-dependent diol dehydratase of Klebsiella oxytoca is apparently not stereospecific and catalyzes the conversion of both (R)- and (S)-1,2-propanediol to propionaldehyde. To explain this unusual property of the enzyme, we analyzed the crystal structures of diol dehydratase in complexes with cyanocobalamin and (R)- or (S)-1,2-propanediol. (R)- and (S)-isomers are bound in a symmetrical manner, although the hydrogen-bonding interactions between the substrate and the active-site residues are the same. From the position of the adenosyl radical in the modeled "distal" conformation, it is reasonable for the radical to abstract the pro-R and pro-S hydrogens from (R)- and (S)-isomers, respectively. The hydroxyl groups in the substrate radicals would migrates from C(2) to C(1) by a suprafacial shift, resulting in the stereochemical inversion at C(1). This causes 60 degrees clockwise and 70 degrees counterclockwise rotations of the C(1)-C(2) bond of the (R)- and (S)-isomers, respectively, if viewed from K+. A modeling study of 1,1-gem-diol intermediates indicated that new radical center C(2) becomes close to the methyl group of 5'-deoxyadenosine. Thus, the hydrogen back-abstraction (recombination) from 5'-deoxyadenosine by the product radical is structurally feasible. It was also predictable that the substitution of the migrating hydroxyl group by a hydrogen atom from 5'-deoxyadenosine takes place with the inversion of the configuration at C(2) of the substrate. Stereospecific dehydration of the 1,1-gem-diol intermediates can also be rationalized by assuming that Asp-alpha335 and Glu-alpha170 function as base catalysts in the dehydration of the (R)- and (S)-isomers, respectively. The structure-based mechanism and stereochemical courses of the reaction are proposed.

About this Structure

1UC4 is a Protein complex structure of sequences from Klebsiella oxytoca with , , and as ligands. Active as Propanediol dehydratase, with EC number 4.2.1.28 Full crystallographic information is available from OCA.

Reference

Structural rationalization for the lack of stereospecificity in coenzyme B12-dependent diol dehydratase., Shibata N, Nakanishi Y, Fukuoka M, Yamanishi M, Yasuoka N, Toraya T, J Biol Chem. 2003 Jun 20;278(25):22717-25. Epub 2003 Apr 8. PMID:12684496

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