1r6d

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{{STRUCTURE_1r6d| PDB=1r6d | SCENE= }}
{{STRUCTURE_1r6d| PDB=1r6d | SCENE= }}
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'''Crystal Structure of DesIV double mutant (dTDP-glucose 4,6-dehydratase) from Streptomyces venezuelae with NAD and DAU bound'''
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===Crystal Structure of DesIV double mutant (dTDP-glucose 4,6-dehydratase) from Streptomyces venezuelae with NAD and DAU 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.
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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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:08:19 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:56:55 2008''

Revision as of 06:57, 29 July 2008

Template:STRUCTURE 1r6d

Crystal Structure of DesIV double mutant (dTDP-glucose 4,6-dehydratase) from Streptomyces venezuelae with NAD and DAU bound

Template:ABSTRACT PUBMED 14570895

About this Structure

1R6D is a Single protein structure of sequence from Streptomyces venezuelae. Full crystallographic information is available from OCA.

Reference

High resolution X-ray structure of dTDP-glucose 4,6-dehydratase from Streptomyces venezuelae., Allard ST, Cleland WW, Holden HM, J Biol Chem. 2004 Jan 16;279(3):2211-20. Epub 2003 Oct 21. PMID:14570895

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