1rkx
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(New page: 200px<br /><applet load="1rkx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rkx, resolution 1.80Å" /> '''Crystal Structure at...)
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Revision as of 20:44, 24 November 2007
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Crystal Structure at 1.8 Angstrom of CDP-D-glucose 4,6-dehydratase from Yersinia pseudotuberculosis
Overview
CDP-D-glucose 4,6-dehydratase catalyzes the conversion of CDP-D-glucose to, CDP-4-keto-6-deoxyglucose in an NAD(+)-dependent manner. The product of, this conversion is a building block for a variety of primary antigenic, determinants in bacteria, possibly implicated directly in reactive, arthritis. Here, we describe the solution of the high-resolution crystal, structure of CDP-D-glucose 4,6-dehydratase from Yersinia, pseudotuberculosis in the resting state. This structure represents the, first CDP nucleotide utilizing dehydratase of the short-chain, dehydrogenase/reductase (SDR) family to be determined, as well as the, first tetrameric structure of the subfamily of SDR enzymes in which NAD(+), undergoes a full reaction cycle. On the basis of a comparison of this, structure with structures of homologous enzymes, a chemical mechanism is, proposed in which Tyr157 acts as the catalytic base, initiating hydride, transfer by abstraction of the proton from the sugar 4'-hydroxyl., Concomitant with the removal of the proton from the 4'-hydroxyl oxygen, the sugar 4'-hydride is transferred to the B face of the NAD(+) cofactor, forming the reduced cofactor and a CDP-4-keto-d-glucose intermediate. A, conserved Lys161 most likely acts to position the NAD(+) cofactor so that, hydride transfer is favorable and/or to reduce the pK(a) of Tyr157., Following substrate oxidation, we propose that Lys134, acting as a base, would abstract the 5'-hydrogen of CDP-4-keto-D-glucose, priming the, intermediate for the spontaneous loss of water. Finally, the resulting, Delta(5,6)-glucoseen intermediate would be reduced suprafacially by the, cofactor, and reprotonation at C-5' is likely mediated by Lys134.
About this Structure
1RKX is a Single protein structure of sequence from Yersinia pseudotuberculosis with NAD as ligand. Active as CDP-glucose 4,6-dehydratase, with EC number 4.2.1.45 Full crystallographic information is available from OCA.
Reference
Crystal structure at 1.8 A resolution of CDP-D-glucose 4,6-dehydratase from Yersinia pseudotuberculosis., Vogan EM, Bellamacina C, He X, Liu HW, Ringe D, Petsko GA, Biochemistry. 2004 Mar 23;43(11):3057-67. PMID:15023057
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