Enzymatic and structural characterization of rTSγ provides insights into the function of rTSβ.
Enzymatic and structural characterization of rTSγ provides insights into the function of rTSβ.
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DOI：
10.1021/bi500349e
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发表时间：
2014-04-29
期刊：
影响因子：
2.9
通讯作者：
Gerlt JA
中科院分区：
文献类型：
--
作者：
Wichelecki DJ;Froese DS;Kopec J;Muniz JR;Yue WW;Gerlt JA
在人类中，编码反向胸苷酸合酶（RT）的基因在编码胸腺层合酶（TS）的相反方向上，与DNA生物合成有关。尽管超过20年在研究中，没有生化的RT同工型在本研究中是生化的，我们将RTSγ鉴定为L-uconate脱水酶，并确定了其高分辨率的晶体结构。
In humans, the gene encoding a reverse thymidylate synthase (rTS) is transcribed in the reverse direction of the gene encoding thymidylate synthase (TS) that is involved in DNA biosynthesis. Three isoforms are found: α, β, and γ, with the transcript of the α-isoform overlapping with that of TS. rTSβ has been of interest since the discovery of its overexpression in methotrexate and 5-fluorouracil resistant cell lines. Despite more than 20 years of study, none of the rTS isoforms have been biochemically or structurally characterized. In this study, we identified rTSγ as an l-fuconate dehydratase and determined its high-resolution crystal structure. Our data provide an explanation for the observed difference in enzymatic activities between rTSβ and rTSγ, enabling more informed proposals for the possible function of rTSβ in chemotherapeutic resistance.
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影响因子：
4.4
作者：
Liang, Ping;Nair, Jayakumar R;Song, Lei;McGuire, John J;Dolnick, Bruce J
通讯作者：
Dolnick, Bruce J
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1385/1-59745-266-1:215
发表时间：
2007-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Vonrhein, Clemens;Blanc, Eric;Bricogne, Gerard
通讯作者：
Bricogne, Gerard
影响因子：
11.2
作者：
Dolnick, R;Wu, Q;Dolnick, BJ
通讯作者：
Dolnick, BJ
影响因子：
14.9
作者：
DOLNICK, BJ
通讯作者：
DOLNICK, BJ