2fty
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(New page: 200px<br /><applet load="2fty" size="350" color="white" frame="true" align="right" spinBox="true" caption="2fty, resolution 2.40Å" /> '''Crystal structure of...)
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Revision as of 17:44, 29 January 2008
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Crystal structure of dihydropyrimidinase from Saccharomyces kluyveri
Overview
In eukaryotes, dihydropyrimidinase catalyzes the second step of the, reductive pyrimidine degradation, the reversible hydrolytic ring opening, of dihydropyrimidines. Here we describe the three-dimensional structures, of dihydropyrimidinase from two eukaryotes, the yeast Saccharomyces, kluyveri and the slime mold Dictyostelium discoideum, determined and, refined to 2.4 and 2.05 angstroms, respectively. Both enzymes have a, (beta/alpha)8-barrel structural core embedding the catalytic di-zinc, center, which is accompanied by a smaller beta-sandwich domain. Despite, loop-forming insertions in the sequence of the yeast enzyme, the overall, structures and architectures of the active sites of the, dihydropyrimidinases are strikingly similar to each other, as well as to, those of hydantoinases, dihydroorotases, and other members of the, amidohydrolase superfamily of enzymes. However, formation of the, physiologically relevant tetramer shows subtle but nonetheless significant, differences. The extension of one of the sheets of the beta-sandwich, domain across a subunit-subunit interface in yeast dihydropyrimidinase, underlines its closer evolutionary relationship to hydantoinases, whereas, the slime mold enzyme shows higher similarity to the noncatalytic, collapsin-response mediator proteins involved in neuron development., Catalysis is expected to follow a dihydroorotase-like mechanism but in the, opposite direction and with a different substrate. Complexes with, dihydrouracil and N-carbamyl-beta-alanine obtained for the yeast, dihydropyrimidinase reveal the mode of substrate and product binding and, allow conclusions about what determines substrate specificity, stereoselectivity, and the reaction direction among cyclic, amidohydrolases.
About this Structure
2FTY is a Single protein structure of sequence from Lachancea kluyveri with as ligand. Active as Dihydropyrimidinase, with EC number 3.5.2.2 Full crystallographic information is available from OCA.
Reference
The crystal structures of dihydropyrimidinases reaffirm the close relationship between cyclic amidohydrolases and explain their substrate specificity., Lohkamp B, Andersen B, Piskur J, Dobritzsch D, J Biol Chem. 2006 May 12;281(19):13762-76. Epub 2006 Mar 3. PMID:16517602
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