Structural Insights into the Drosophila melanogaster Retinol Dehydrogenase, a Member of the Short-Chain Dehydrogenase/Reductase Family.
Structural Insights into the Drosophila melanogaster Retinol Dehydrogenase, a Member of the Short-Chain Dehydrogenase/Reductase Family.
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对果蝇的结构见解，果蝇脱氢酶，短链脱氢酶/还原酶家族的成员。
DOI：
10.1021/acs.biochem.6b00907
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发表时间：
2016-11-29
期刊：
影响因子：
2.9
通讯作者：
Palczewski, Krzysztof
中科院分区：
文献类型：
--
作者：
Hofmann, Lukas;Tsybovsky, Yaroslav;Alexander, Nathan S.;Babino, Darwin;Leung, Nicole Y.;Montell, Craig;Banerjee, Surajit;von Lintig, Johannes;Palczewski, Krzysztof
视色素的11-顺式-亚视黄基发色团在与光子相互作用时异构化，启动下游级联信号事件，最终导致视觉感知。11-顺式-视黄基通过酶促转化再生，统称为视觉循环。该循环中的第一个限速酶促反应，即，全反式-视黄醛还原为全反式-视黄醇是由视黄醇脱氢酶催化的。在这里，我们确定了果蝇感光视黄醇脱氢酶（PDH）亚型C的结构，属于短链脱氢酶/还原酶（SDR）家族。这是第一个报道的SDR结构，具有这种生物学上重要的活性。在不同条件下生长的相同酶的两种晶体结构揭示了NAD+辅因子的新构象变化，可能代表了催化过程中的变化。PDH的酰胺氢-氘交换证明了二核苷酸结合后酶结构的变化。In D.在黑腹动物中，PDH活性的丧失导致光感受器变性，其可以通过人RDH 12的转基因表达而部分挽救。基于PDH的结构，我们分析了在人类RDH 12同源模型中导致Leber先天性黑蒙13的突变，以深入了解RDH 12致病突变的分子基础。
The 11-cis-retinylidene chromophore of visual pigments isomerizes upon interaction with a photon, initiating a downstream cascade of signaling events that ultimately lead to visual perception. 11-cis-Retinylidene is regenerated through enzymatic transformations collectively called the visual cycle. The first and rate-limiting enzymatic reaction within this cycle, i.e., the reduction of all-trans-retinal to all-trans-retinol, is catalyzed by retinol dehydrogenases. Here, we determined the structure of Drosophila melanogaster photoreceptor retinol dehydrogenase (PDH) isoform C that belongs to the short-chain dehydrogenase/reductase (SDR) family. This is the first reported structure of a SDR that possesses this biologically important activity. Two crystal structures of the same enzyme grown under different conditions revealed a novel conformational change of the NAD+ cofactor, likely representing a change during catalysis. Amide hydrogen–deuterium exchange of PDH demonstrated changes in the structure of the enzyme upon dinucleotide binding. In D. melanogaster, loss of PDH activity leads to photoreceptor degeneration that can be partially rescued by transgenic expression of human RDH12. Based on the structure of PDH, we analyzed mutations causing Leber congenital amaurosis 13 in a homology model of human RDH12 to obtain insights into the molecular basis of RDH12 disease-causing mutations.
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影响因子：
4.4
作者：
Cossi, M;Barone, V
通讯作者：
Barone, V
影响因子：
5.6
作者：
Benach, J;Atrian, S;Ladenstein, R
通讯作者：
Ladenstein, R
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
DOI：
10.1093/bioinformatics/btq662
发表时间：
2011-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Benkert P;Biasini M;Schwede T
通讯作者：
Schwede T
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC