2po3
From Proteopedia
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Crystal Structure Analysis of DesI in the presence of its TDP-sugar product
Overview
Desosamine is a 3-(dimethylamino)-3,4,6-trideoxyhexose found, for example, in such macrolide antibiotics as erthyromycin, azithromycin, and, clarithromycin. The efficacies of these macrolide antibiotics are markedly, reduced in the absence of desosamine. In the bacterium Streptomyces, venezuelae, six enzymes are required for the production of, dTDP-desosamine. The focus of this X-ray crystallographic analysis is the, third enzyme in the pathway, a PLP-dependent aminotransferase referred to, as DesI. The structure of DesI was solved in complex with its product, dTDP-4-amino-4,6-dideoxyglucose, to a nominal resolution of 2.1 A. Each, subunit of the dimeric enzyme contains 12 alpha-helices and 14, beta-strands. Three cis-peptides are observed in each subunit, Phe 330, Pro 332, and Pro 339. The two active sites of the enzyme are located in, clefts at the subunit/subunit interface. Electron density corresponding to, the bound product clearly demonstrates a covalent bond between the amino, group of the product and C-4' of the PLP cofactor. Interestingly, there, are no hydrogen-bonding interactions between the protein and the, dideoxyglucosyl group of the product (within 3.2 A). The only other, sugar-modifying aminotransferase whose structure is known in the presence, of product is PseC from Helicobacter pylori. This enzyme, as opposed to, DesI, catalyzes amino transfer to the axial position of the sugar. A, superposition of the two active sites for these proteins reveals that the, major differences in ligand binding occur in the orientations of the, deoxyglucosyl and phosphoryl groups. Indeed, the nearly 180 degrees, difference in hexose orientation explains the equatorial versus axial, amino transfer exhibited by DesI and PseC, respectively.
About this Structure
2PO3 is a Single protein structure of sequence from Streptomyces venezuelae with as ligand. Full crystallographic information is available from OCA.
Reference
Molecular Architecture of DesI: A Key Enzyme in the Biosynthesis of Desosamine(,)., Burgie ES, Holden HM, Biochemistry. 2007 Aug 7;46(31):8999-9006. Epub 2007 Jul 13. PMID:17630700
Page seeded by OCA on Wed Jan 23 14:12:49 2008
