1f8x
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(New page: 200px<br /><applet load="1f8x" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f8x, resolution 2.5Å" /> '''CRYSTAL STRUCTURE OF ...)
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Revision as of 12:35, 20 November 2007
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CRYSTAL STRUCTURE OF NUCLEOSIDE 2-DEOXYRIBOSYLTRANSFERASE
Overview
BACKGROUND: Nucleoside 2-deoxyribosyltransferase plays an important role, in the salvage pathway of nucleotide metabolism in certain organisms, catalyzing the cleavage of beta-2'-deoxyribonucleosides and the subsequent, transfer of the deoxyribosyl moiety to an acceptor purine or pyrimidine, base. The kinetics describe a ping-pong-bi-bi pathway involving the, formation of a covalent enzyme-deoxyribose intermediate. The enzyme is, produced by a limited number of microorganisms and its functions have been, exploited in its use as a biocatalyst to synthesize nucleoside analogs of, therapeutic interest. RESULTS: We describe the crystal structure of the, enzyme with and without bound ligand. The native structure was solved by, the single isomorphous replacement with anomalous scattering method, (SIRAS) and refined to 2.5 A resolution resulting in a crystallographic R, factor of 16.6%. The enzyme comprises a single domain that belongs to the, general class of doubly-wound alpha/beta proteins; it also exhibits a, unique nucleoside-binding motif. X-ray analysis of enzyme-purine and, enzyme-pyrimidine complexes presented here reveals that the active site, lies in a cleft formed by the edge of the beta sheet and two alpha helices, and contains side chains from two subunits. CONCLUSIONS: These results, indicate residues that may be important in substrate binding and catalysis, and thus may serve as a framework for elucidating the mechanism of enzyme, activity. In particular, the proposed nucleophile, Glu98, lies in the, nucleoside-binding pocket at an appropriate position for nucleophilic, attack. A comparison of the enzyme interactions with both a purine and, pyrimidine ligand provides some insight into the structural basis for, enzyme specificity.
About this Structure
1F8X is a Single protein structure of sequence from Lactobacillus leichmannii. Active as Nucleoside deoxyribosyltransferase, with EC number 2.4.2.6 Full crystallographic information is available from OCA.
Reference
Crystal structures of nucleoside 2-deoxyribosyltransferase in native and ligand-bound forms reveal architecture of the active site., Armstrong SR, Cook WJ, Short SA, Ealick SE, Structure. 1996 Jan 15;4(1):97-107. PMID:8805514
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