摘要
Dehydrogenase/reductase (SDR family) member 3 (DHRS3), also known as retinal short-chain dehydrogenase/reductase (retSDR1) is a member of SDR16C family. This family is thought to be NADP(H) dependent and to have multiple substrates; however, to date, only all-trans-retinal has been identified as a DHRS3 substrate. The reductive reaction catalysed by DHRS3 seems to be physiological, and recent studies proved the importance of DHRS3 for maintaining suitable retinoic acid levels during embryonic development in vivo. Although it seems that DHRS3 is an important protein, knowledge of the protein and its properties is quite limited, with the majority of information being more than 15 years old.
This study aimed to generate a more comprehensive characterisation of the DHRS3 protein. Recombinant enzyme was prepared and demonstrated to be a microsomal, integral-membrane protein with the C-terminus oriented towards the cytosol, consistent with its preference of NADPH as a cofactor. It was determined that DHRS3 also participates in the metabolism of other endogenous compounds, such as androstenedione, estrone, and DL-glyceraldehyde, and in the biotransformation of xenobiotics (e.g., NNK and acetohexamide) in addition to all-trans-retinal. Purified and reconstituted enzyme was prepared for the first time and will be used for further studies. Expression of DHRS3 was shown at the level of both mRNA and protein in the human liver, testis and small intestine. This new information could open other areas of DHRS3 protein research.
摘要译文
脱氢酶/还原酶（SDR家族）成员3（DHRS3），也被称为视网膜短链脱氢酶/还原酶（retSDR1）是SDR16C家族的一个成员。这个家族被认为是NADP（H）依赖和具有多个基板;然而，迄今为止，只有全反式 - 视黄醛已经被确定为一个DHRS3衬底。还原反应通过DHRS3催化似乎是生理性的，并且最近的研究证明了在体内胚胎发育过程中保持适当的视黄酸水平DHRS3的重要性。虽然看上去DHRS3是一个重要的蛋白质，该蛋白质及其性质的知识是相当有限的，大多数的信息是超过15岁。
本研究旨在生成DHRS3蛋白质的更全面的表征。重组酶制备并证明是一个微粒，整体膜蛋白的C末端朝向胞质溶胶，具有NADPH其优先作为辅因子相一致。它被确定DHRS3还参与其他内源性化合物，如雄烯二酮，雌酮，和DL-甘油的代谢，并在生物异源物质（例如，NNK和醋磺）除了全反式 - 视黄醛的生物转化。纯化和重新构成的酶的制备的第一次和将被用于进一步的研究。DHRS3的表达被示出在mRNA在人类肝脏，睾丸和小肠的水平和蛋白质。这种新的信息可以打开DHRS3蛋白质研究的其他领域。
Tereza Lundová[a]; Lucie Zemanová[a]; Beata Malčeková[a]; Adam Skarka[a]; Hana Štambergová[a]; Jana Havránková[a]; Miroslav Šafr[b]; Vladimír Wsól[a]. Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3)[J]. Chemico-Biological Interactions, 2015,234: 178–187