2002
DOI: 10.1074/jbc.m111735200
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Abstract: Nucleoside hydrolases are key enzymes in the purine salvage pathway of Trypanosomatidae and are considered as targets for drug design. We previously reported the first x-ray structure of an inosine-adenosineguanosine preferring nucleoside hydrolase (IAG-NH) from Trypanosoma vivax (1). Here we report the 2.0-Å crystal structure of the slow D10A mutant in complex with the inhibitor 3-deaza-adenosine and the 1.6-Å crystal structure of the same enzyme in complex with a genuine substrate inosine. The enzyme-substra… Show more

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Cited by 57 publications
(131 citation statements)
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“…These results confirm that the second Asp of the DTDPGIDD conserved motif functions as the active site base in plant NRHs. A similar result was reported for the equivalent D10A mutant in TvNRH (Versées et al, 2002), which was between 10 3 and 10 4 times less active than the wildtype enzyme but has an identical K m value.…”
Section: Crystal Structure and Substrate Binding In Plant Nrhssupporting
confidence: 85%
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“…These results confirm that the second Asp of the DTDPGIDD conserved motif functions as the active site base in plant NRHs. A similar result was reported for the equivalent D10A mutant in TvNRH (Versées et al, 2002), which was between 10 3 and 10 4 times less active than the wildtype enzyme but has an identical K m value.…”
Section: Crystal Structure and Substrate Binding In Plant Nrhssupporting
confidence: 85%
“…Three other residues, Asp-250 and Asp-252, both positioned in the loop between helix a11 and strand b5, and Tyr-255, were also targeted in order to determine if more mobile regions are involved in substrate binding, as shown previously for TvNRH (Versées et al, 2002). Circular dichroism spectroscopy measurements indicate that the folding in solution of each mutant variant resembles that of WT-PpNRH1 (Supplemental Fig.…”
Section: Docking Analysis and Site-directed Mutagenesis Of Ppnrh1mentioning
confidence: 92%
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“…However, care must be taken in the interpretation of these kinetic isotope effects because they may be caused by binding rather then catalysis (6). The present study on the purine-specific nucleoside hydrolase (EC 3.2.2.1) of Trypanosoma vivax (TvNH) 1 aims to elucidate the catalytic role of the 5Ј-OH group, which contributes 5.4 kcal/mol to k cat /K m (1).…”
mentioning
confidence: 99%
“…[14][15][16] The analysis of the crystallographic structure of NH from Crithidia fasciculata complexed with p-aminophenyliminoribitol (pAPIR) shows that each NH monomer is functional and contains a narrow and deep active site with a strongly bound Ca 2+ ion. 18,[26][27][28] This cation is octacoordinated by a net of interactions involving the O atoms of the side chains of residues Asp10, Asp15, Asp242, the carbonyl oxygen of the main chain of Thr126, and three water molecules. In the enzyme-substrate complex, two of the water molecules are replaced by the 2' and 3' hydroxyl groups of the substrate ribose.…”
mentioning
confidence: 99%