Crystal structure of 1-deoxy-D-xylulose-5-phosphate reductoisomerase from Zymomonas mobilis at 1.9-Å resolution
Crystal structure of 1-deoxy-D-xylulose-5-phosphate reductoisomerase from Zymomonas mobilis at 1.9-Å resolution
复制标题
DOI：
10.1016/j.bbapap.2003.10.006
复制
发表时间：
2004-04-08
影响因子：
3.2
通讯作者：
Schneider, G
中科院分区：
文献类型：
--
作者：
Ricagno, S;Grolle, S;Schneider, G
1-脱氧-D-木糖-5-磷酸还原异构酶(DXR)是类异戊二烯生物合成非甲戊酸途径中的第二种酶。运动发酵单胞菌的脱辅酶原的结构已被解析并细化到1.9埃分辨率，而共底物NADPH的二元复合体的结构被细化到2.7埃分辨率。DXR的亚基由三个结构域组成。残基1-150形成NADPH结合域，它是典型的二核苷酸结合折叠的变体。第二个结构域包括一个四链的混合P-折叠，在该折叠的两侧有三个螺旋。大多数推测的活性位点残基都位于这个结构域上。C-末端结构域(残基300-386)折叠成四螺旋束。在溶液和晶体中，该酶形成同源二聚体。两个单体之间的界面主要是通过在第二结构域中延伸片层来形成的。NADPH的腺苷磷酸部分以规范的方式与核苷酸结合折叠结合。腺嘌呤环与β1之后的环以及α2和β2之间的环以及α5和β5之间的环相互作用。烟酰胺环在这种二元络合物的晶体中是无序的。与大肠杆菌DXR的比较表明，这两种酶在结构上非常相似，活性部位结构高度保守。然而，这两种酶对NADPH的腺嘌呤环的识别存在差异。(C)2003爱思唯尔B.V.保留所有权利。
1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is the second enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. The structure of the apo-form of this enzyme from Zymomonas mobilis has been solved and refined to 1.9-Angstrom resolution, and that of a binary complex with the co-substrate NADPH to 2.7-Angstrom resolution. The subunit of DXR consists of three domains. Residues 1-150 form the NADPH binding domain, which is a variant of the typical dinucleotide-binding fold. The second domain comprises a four-stranded mixed p-sheet, with three helices flanking the sheet. Most of the putative active site residues are located on this domain. The C-terminal domain (residues 300-386) folds into a four-helix bundle. In solution and in the crystal, the enzyme forms a homo-dimer. The interface between the two monomers is formed predominantly by extension of the sheet in the second domain. The adenosine phosphate moiety of NADPH binds to the nucleotide-binding fold in the canonical way. The adenine ring interacts with the loop after beta1 and with the loops between alpha2 and beta2 and alpha5 and beta5. The nicotinamide ring is disordered in crystals of this binary complex. Comparisons to Escherichia coli DXR show that the two enzymes are very similar in structure, and that the active site architecture is highly conserved. However, there are differences in the recognition of the adenine ring of NADPH in the two enzymes. (C) 2003 Elsevier B.V. All rights reserved.