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| {{STRUCTURE_1r66| PDB=1r66 | SCENE= }} | | {{STRUCTURE_1r66| PDB=1r66 | SCENE= }} |
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| '''Crystal Structure of DesIV (dTDP-glucose 4,6-dehydratase) from Streptomyces venezuelae with NAD and TYD bound'''
| | ===Crystal Structure of DesIV (dTDP-glucose 4,6-dehydratase) from Streptomyces venezuelae with NAD and TYD bound=== |
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| ==Overview==
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| Desosamine is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in some macrolide antibiotics. In Streptomyces venezuelae, there are seven genes required for the biosynthesis of this unusual sugar. One of the genes, desIV, codes for a dTDP-glucose 4,6-dehydratase, which is referred to as DesIV. The reaction mechanisms for these types of dehydratases are quite complicated with proton abstraction from the sugar 4'-hydroxyl group and hydride transfer to NAD+, proton abstraction at C-5, and elimination of the hydroxyl group at C-6 of the sugar, and finally return of a proton to C-5 and a hydride from NADH to C-6. Here we describe the cloning, overexpression, and purification, and high resolution x-ray crystallographic analysis to 1.44 A of wild-type DesIV complexed with dTDP. Additionally, for this study, a double site-directed mutant protein (D128N/E129Q) was prepared, crystallized as a complex with NAD+ and the substrate dTDP-glucose and its structure determined to 1.35 A resolution. In DesIV, the phenolate group of Tyr(151) and O(gamma) of Thr(127) lie at 2.7 and 2.6 A, respectively from the 4'-hydroxyl group of the dTDP-glucose substrate. The side chain of Asp(128) is in the correct position to function as a general acid for proton donation to the 6'-hydroxyl group while the side chain of Glu(129) is ideally situated to serve as the general base for proton abstraction at C-5. This investigation provides further detailed information for understanding the exquisite chemistry that occurs in these remarkable enzymes.
| | The line below this paragraph, {{ABSTRACT_PUBMED_14570895}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 14570895 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_14570895}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Rossmann fold]] | | [[Category: Rossmann fold]] |
| [[Category: Short-chain dehydrogenase/reductase]] | | [[Category: Short-chain dehydrogenase/reductase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:07:58 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:03:50 2008'' |
