Tsigelny I, Baker M E
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093, USA.
Biochem Biophys Res Commun. 1995 Dec 26;217(3):859-68. doi: 10.1006/bbrc.1995.2851.
Human 11 beta-hydroxysteroid dehydrogenase-types 1 and 2 and human 15-hydroxyprostaglandin dehydrogenase belong to a large family of oxidoreductases that includes human dihydropteridine reductase and Streptomyces hydrogenans 20 beta-hydroxysteroid dehydrogenase, for which 3D structures are available. Almost all of these enzymes are either dimers or tetramers. The dimer interface of rat dihydropteridine reductase consists of alpha-helices E and F from each monomer arranged in a four alpha-helix bundle [Varughese et al. (1992) Proc. Natl. Acad. Sci. USA 89, 6080-6084]. Alpha-helix F contains tyrosine-146 and lysine-150, residues that are highly conserved in this protein superfamily and have been proposed to be at the catalytic site. We have examined the dimer interface between alpha-helix F in human and rat dihydropteridine reductase and Streptomyces hydrogenans 20 beta-hydroxysteroid dehydrogenase as well as modeled 3D structures of steroid and prostaglandin dehydrogenases and homologs for stabilizing interactions. We find a site in the middle of alpha-helix F that stabilizes the dimer. This anchor is adjacent to conserved lysine on alpha-helix F. Our analysis suggests that sequence variation in the anchor may be important in substrate specificity.
人类11β-羟基类固醇脱氢酶1型和2型以及人类15-羟基前列腺素脱氢酶属于一个氧化还原酶大家族，该家族包括人类二氢蝶啶还原酶和链霉菌氢化酶20β-羟基类固醇脱氢酶，它们都有三维结构。几乎所有这些酶都是二聚体或四聚体。大鼠二氢蝶啶还原酶的二聚体界面由每个单体的α-螺旋E和F组成，排列成一个四螺旋束[瓦鲁盖斯等人（1992年）《美国国家科学院院刊》89，6080 - 6084]。α-螺旋F包含酪氨酸-146和赖氨酸-150，这些残基在这个蛋白质超家族中高度保守，并且被认为位于催化位点。我们研究了人类和大鼠二氢蝶啶还原酶以及链霉菌氢化酶20β-羟基类固醇脱氢酶中α-螺旋F之间的二聚体界面，并对类固醇和前列腺素脱氢酶及其同源物的三维结构进行建模以稳定相互作用。我们在α-螺旋F的中间发现了一个稳定二聚体的位点。这个锚定区域与α-螺旋F上保守的赖氨酸相邻。我们的分析表明，锚定区域的序列变异可能在底物特异性方面很重要。
